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Overview of Nuclear Medicine Techniques

Nuclear medicine is a medical field that utilizes radioactive materials for disease diagnosis and treatment, involving techniques such as SPECT and PET imaging. It covers various aspects including radionuclide tracing, instrumentation, radiopharmaceuticals, and specific applications in endocrinology and organ imaging. Key concepts include radiation decay, principles of radiation protection, and clinical applications for conditions like thyroid disorders and cancer detection.
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0% found this document useful (0 votes)
81 views906 pages

Overview of Nuclear Medicine Techniques

Nuclear medicine is a medical field that utilizes radioactive materials for disease diagnosis and treatment, involving techniques such as SPECT and PET imaging. It covers various aspects including radionuclide tracing, instrumentation, radiopharmaceuticals, and specific applications in endocrinology and organ imaging. Key concepts include radiation decay, principles of radiation protection, and clinical applications for conditions like thyroid disorders and cancer detection.
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd

Nuclear medicine

Chapter 1 General part


Nuclear medicine: A branch of medicine concerned with the use of radioactive materials in the
diagnosis and treatment of disease and medical research.
SPECT ——single photon emission computed tomography
PET ——positron emission tomography
Radionuclide( unstable nuclide):
It refers to the unstable nuclei spontaneously emit radiation (such as alpha, beta ray)to form stable
nuclei by decay.
Isotopes:
The isotopes of an element are having the same protons but different neutrons. Isotopes have
similar chemical properties.
Isomers:
Isomers are nuclides having the same number of protons and neutrons , but different energy
state.(99mTc , 99Tc )
Nuclide:
A nuclide is any individual atomic species, characterized by a specific number of neutrons and
protons and energy state.
Radiation decay :
Alpha(α) decay
Beta-minus decay
Beta-plus decay
Electron capture
Gamma(γ) decay
Interaction of charged particles with matter:
Ionization
Excitation
Scattering
Absorption
annihilation radiation
Interaction of photons with matter:
Photoelectric absorption
Compton scattering
Pair production
half-life
T1/2 : the half-life of the radionuclide.
a time period that the number of nuclei decreases by one-half.
Radioactivity is measured in units of becquerel (Bq).
Radiation effects:
determinate effects
stochastic effects
Principles of radiation protection :
Justification
Optimization
Individual dose and risk limitation
External radiation protection measures:
Time
Distance
Shielding

Chapter 2 Radionuclide Tracing Technique and Organ Imaging


the types and characteristics of the imaging:
1. static imaging
the distribution of the imaging agent in organs and lesions is stable when the imaging is
carried out.
2. dynamic imaging
After the imaging agent is introduced into the body, the continuous imaging of the dynamic
collecting organ is quickly carried out with preset speed.
3. early imaging
Imaging be occurred within 2 h after injection of the imaging agent.
mainly reflects the organ perfusion and early functional status.
[Link] imaging
Imaging be occurred 2 hours and above after injection of the imaging agent.
5. positive imaging (hot spot imaging)
Imaging agent is mainly uptaken by the lesion tissue, and generally not or rarely by normal
[Link] radioactivity of the lesion was higher than that of the normal tissue, show "hot spot"
changes.
6. negative imaging (cold zone imaging)
The imaging agent is mainly in the normal tissue uptake, while the pathological tissue is not
uptaken, the performance of the radioactive distribution is sparse or defect in static imaging.

Chapter 3 Nuclear medicine instrumentation


Nuclear medicine instrumentation means some special systems, which measure and detect the
amount or number of ionizations or excitation events.
The scintillation detectors are mainly composed of :
scintillators,
photomultiplier tube
preamplifier.
Positron Emission Tomography ,also called PET imaging , is a nuclear medicine technology that
uses short-lived radionuclide attached to biological molecules to allow the visualization of
metabolic processes in the body by producing an image of the distribution.
Comparison of PET and SPECT
Chapter 4 Radiopharmaceuticals
Definition of a radiopharmaceutical
A radiopharmaceutical is a radioactive compound used for the diagnosis and therapeutic treatment
of human diseases. A radiopharmaceutical has two components: a radionuclide and a
pharmaceutical.
Main features of radiopharmaceuticals:
1. Radioactive
2. Unconstant
3. Self radiation decomposition
4. Few amount
Production of radionuclides:
1. Nuclear reactor
2. Cyclotron
3. Radionuclide generator
Ideal radiopharmaceutical:
Easy availability
Short effective half-life
Particle emission
Suitable energy
High target-to-nontarget activity ratio
Radionuclidic purity: the fraction of the total radioactivity in the form of the desired radionuclide
present in a radiopharmaceutical
Radiochemical purity: the fraction of the total radioactivity in the desired chemical form in the
radiopharmaceutical.

Chapter 5 Nuclear Endocrinology (NE)


Most commonly used isotopes in thyroid:
99Tcm , Technetium-99m
131I, Radioiodine-131
123I, Radioiodine-123

99Tcm (99Tcm O4-)


pure gamma emitter
energy 140 keV
half-life 6 hours
it is not organified after trapping, it is relatively quickly released back to the blood
Used for imaging only
131I:
delivers both beta and gamma radiation
gamma energy is 364 keV
half-life is 8 days
used for
Thyroid uptake test
Thyroid imaging
Therapy
123I
pure gamma radiator
energy of 159 keV
half-life is 13 hours
it has ideal properties for imaging but its cost is high
used for imaging only
Radioactive iodide uptake (RAIU) is the percentage of administered radioiodine incorporated by
the thyroid gland.
formula to calculate RAIU:
Normal: Uptake increases with time and the peak at about 24hrs
GD: Uptake higher than normal and the peaktime less than 24h
Increased I-131 Uptake Diseases:
Graves’ Disease
Toxic multi-nodular goitre
Solitary hyper-functioning nodule
Decreased I-131 Uptake Diseases :
Hypothyroidism: Primary or Secondary, Surgical/Radioiodine Ablation of Thyroid
Thyroiditis: Acute, Subacute and Chronic Lymphocytic
Renal failure, congestive heart failure: increased iodide retention
Clinical indications:
To determine the functional status of the thyroid gland
To calculate specific doses of 131I for the treatment of hyperthyroidism
To differentiate subacute or painless thyroiditis and factitious hyperthyroidism from Graves’
disease
T3, T4 and RAIU separation, parallel
Clinical contraindications:
Pregnancy
Nursing status
Thyroid Scintigraphy:
Clinical applications:
Localization of Ectopic Thyroid Gland
Determination of Nodule Function
Differentiate Diagnosis of benign from malignant
Differentiate Diagnosis of neck mass
Detection of thyroid cancer metastasis
Evaluation of thyroid weight
Thyroid nodule:
cold nodule demonstrates decreased (absent) tracer uptake compared to the surrounding normal
thyroid tissue. Malignancy is 10%~25%.
hot nodule has greater more activity than the normal surrounding thyroid tissue.
warm nodule has activity equal to the adjacent thyroid gland.
Genitourinary System
1, renogram:
3 phases of normal renogram:
phase a(arrival of tracer)
phase b(concentration)
phase c(elimination)
Quantitive analysis:
peak time(tb)<4.5min
half time(C1/2)<8min
15min residue rate<50%
difference between peak time<1min
difference between peak value<30%
Glomerular filtration rate(GFR): The plasma volume(ml) filtrated through the glomerulus
per minute .Normal value: 80-100 ml/min.

2, dynamic renal imaging :


Radiopharmaceuticals:
Glomerular filtration: 99mTc-DTPA
Renal tubular epithelial secretion: 131I-OIH
Seven types of abnormal curve:
Prabola type
Low level prolonged type
Low level descending type
Acute rising type
High level prolonged type
Stepwise drop type
Small kidney type
Clinical applicance of dynamic renal imaging :
Renal Artery Stenosis
Infection
Obstruction
Transplant
NUCLEAR MEDICINE
1: What is the definition of nuclear medicine?
A branch of medicine concerned with use of radioactive material in the diagnosis and treatment of
disease and medical research.

2: What are the modes of radiation decay?


1) Alpha decay 2) Beta decay 3) Beta-plus decay 4) Electron capture 5) Gamma decay.

3: The concept of T1/2and Teff?


T1/2: the half life of the radionuclide. A time period that the number of the nuclei decreases by one half.
1/Teff=1/Tp+1/Tb

4: The concept of Radioactivity and the units?


The size or weight of the quantity of material does not indicate how much radioactivity is present.
Radioactivity is measured in units of Becquerel (Bq). 1 Bq = 1 event of radiation emission per second.
1 Ci = 3.7×1010 Bq.

5: The concept of determinate effects and stochastic effects?


Determinate effects: The severity of the effect varies with the dose and the effects are not seen below a
certain threshold level of radiation.
Stochastic effects: These effects have no threshold and the severity of the effects does not vary with the
does. The probability of occurrence however increases as the dose increases.

6: What are the principles of radiation protection?


1) Justification: No practice involving exposure to radiation should be adopted unless it produces
enough benefit to the exposed individuals or to the society to offset the radiation detriment it causes.
2) Optimization: Exposures to radiation should be as low as reasonably achievable.
3) Individual dose and risk limitation: No individual should receive radiation doses higher than
maximum allowable limits.

7: What are basics of external radiation protection?


1) Time: The amount of radiation exposure increases and decreases with the time people spend near the
source of radiation.
2) Distance: As a rule, if you double the distance, you reduce the exposure by a factor of four.
3) The greater the shielding around a radiation source, smaller the exposure.
8: What is PET?
Positron Emission Tomography is the innovative medical imaging technology for the detection of
cancers, brain disorders and heart diseases. PET provides quantitative biochemical information such as
metabolism, blood flow, blood volume. PET can find unsuspected disease earlier and more accurate
than CT 0r MRI.

9: What is the cause of PET image artifacts?


1) Patient Motion: such as respiratory motion.
2) Displacement of organs and bowel by bladder or rectal filling.
3) IV contrast and Oral contrast (barium).
4) Metallic hardware: Metal implants associated with chemotherapy ports, artificial joints or dental
fillings.
5) Cardiac Pacers
6) Subcutaneous infiltration of the tracer.

10: What is SUV?


SUV means selected region activity (mCi/ml)/ [injected dose (mCi)/body weight (kg)]

11: What are the factors affecting SUV measurement?


1) Plasma glucose levels.
2) Time after FDG injection.
3) Subcutaneous infiltration of the tracer.
4) Body weight or body surface area.
5) Size of the region of interest.
6) Resolution of the scanner.
7) Type of image reconstruction and attenuation correction.
8) Patient motion (due to lesion blurring).

12: What are indications for 18F-FDG PET/CT?


1) Differentiating benign from malignant lesions.
2) Searching for an unknown primary tumor.
3) Staging known malignancies.
4) Monitoring the effect of therapy on known malignancies.
5) Determining whether residual abnormalities represent tumor or post treatment fibrosis or necrosis.
6) Detecting tumor recurrence especially in the presence of elevated levels of tumors markers.
7) Selecting the region of a tumor most likely to yield diagnostic information for biopsy.
8) Guiding radiation therapy planning.
9) Nononcologic applications, such as evaluation of infection and atherosclerosis.
13. What is the clinical indication ofRAIU TEST?

 To determine the functional status of the thyroid gland


 To calculate specific doses for the treatment of hyperthyroidism
 To differentiate subacute or painless thyroiditis and factitious hyperthyroidism from Graves’
disease.

14. Perchlorate Discharge Test?

 Indicated the presence of a defect of iodide organification.

15. What is the Radiopharmaceuticals &Clinical Application of thyroid scintigraphy?

Radiopharmaceuticals

Most common: 99TcmO4- , 123I, 131I,

Tumor positive: 18F-FDG, 99Tcm-MIBI, 201Tl

Clinical Application of thyroid scintigraphy

1. Localization of Ectopic Thyroid Gland.


2. Determination of Nodule Function.
3. Differentiate Diagnosis of benign from malignant .
4. Differentiate Diagnosis of neck mass.
5. Detection of thyroid cancer metastasis.
6. Evaluation of thyroid weight.

16. What is the Parathyroid Scintigraphy Methods&Clinical Application?

 Parathyroid Scintigraphy Methods (2) :

 Subtraction imaging

 Dual-phase imaging

 Clinical Application
 localizing of the hyperfunctioning parathyroid gland (adenoma or hyperplasia) before
surgery for shortening operation time.

17. Contrast between adrenal cortex and adrenal medulla imaging?

Adrenal Cortex Imaging Adrenal Medulla Imaging


131 123
Radiopharm I-6-IC I-/131I-MIBG
Clinical Application study of adrenocortical hyperfunction localizing Pheochromocytoma,
neuroblastoma, carcinoids and
medullary thyroid carcinomas
18. What is Comparison between bone scan and radiography (X-ray)?

Methods Parameter of Time of Extension of Resolu-tion


Measurement revealment visualization
X-ray Anatomy Changes of region better
skeletal
Calcification
>30%
Bone scan blood flow, 3-6 months earlier whole body bone worse
metabolism than above

19. What are the Super Scan & its clinical application?

Super Scan
very high concentration in bones, very little in soft tissues, no images in both kidneys and bladder.
Clinical significance
 Extensive bone metastasis of malignancy.
 Hyperparathyroidism.

20. What is the Flare phenomenon?

More foci in the image with improving symptoms after the first period of treatment.

Less foci with more improved symptoms after the second period of treatment.

21. What is the Clinical application of bone scan?

Diagnosis of

 metastatic malignant bone tumors (most common)


 metabolic bone diseases
 ischemic necrosis of caput ossis femoris
 acute osteomyelitis
 fracture
 Paget’s disease
 And
 determination of involvement of primary bone tumors and therapeutic effect
 monitoring bone transplant and prosthesis.
22. What is the clinical application of Hepatobiliary dynamic imaging?

 Diagnose:
– Congenital biliary atresia or hepatitis in neonate
– Acute cholecystitis
– Obstruction of common bile duct
 And
– postoperative follow up of biliary tract

23. What is the analysis of Renogram?

Analysis

 3 portions of normal renogram


– portion a(arrival of tracer)
– portion b(concentration)
– portion c(elimination)
 Quantitive analysis
 Looking at the peak time (tb),
 Identify the half-time (C1/2)
 Residue rate (% of original concentration)
 Then you calculate the difference between peak time, and peak value.

24. What is the clinical application of Renogram?

 Diagnosis of urinary tract obstruction


 Determination of each renal function
 Determination of renovascular hypertension
 Monitering kidney transplantation.
 Others.

25. What is clinical application of myocardial perfusion imaging?


1. Diagnosis, risk stratification and outcome evaluation of CAD
2. Evaluation of myocardial viability
3. Evaluation of myocardial infarction
4. Evaluation of intermediate lesions
5. Assessment of treatment of PCI or CABG
6. Prediction of heart events before no-heart surgery
7. Diagnosis of cardiomyopathy or myocarditis.

26. What are the stress and abnormal pet/SPECT? or compare b/w these terms?
 Reversible defect:myocardial ischemia
 Fixed defect:myocardial infarction or scar tissue or severe myocardial ischemia
 Mixed defect:myocardial ischemia and myocardial infarction
 Tinea sample change :cardiomyopathy or myocarditis
 reverse redistribution :unknown reasona
27. Clinical indication of rCBF(regional cerebral blood flow)?
 Detection and evaluation of cerebrovascular disease
 Stroke
 Transient ischemic attacks(TIA)
 Subarachnoid hemorrhage(SAH)
 Arteriovenous malformation(AVM)
 Other derangements of cerebral hemodynamics
 Management of a patient with epilepsy
 Evaluation of patients with suspected dementia
 Evaluation of brain tumor
 Anxiety disorders and affective disorders
 Addictions
 Management of patients with schizophrenia
 Management of patients with movement disorders

28. What is the Luxury perfusion and Crossed diaschisis?

 Luxury perfusion: Abnormal hyperperfusion around the infarct foci.


 Crossed diaschisis: When one side cerebrum cortex has low or defect radioactivity areas, the
other side cerebrum or cerebellum has foci, too.

29. What is Radionuclide therapy?


 is a form of radiotherapy useing unsealed radionuclide as radiation sources for the
selective delivery of radiation to tumours or target organs. By virtue of ionizing
properties of radiation, radionuclide achieves its therapeutic purposes.

30. Which radiation could be used in radionuclide therapy?

 There are three types of particulate radiation of consequence for targeted radionuclide
therapy—beta particles, alpha particles, and Auger electrons—which can irradiate tissue
volumes with multicellular, cellular and subcellular dimensions,respectively.

[Link] are the Radioiodine Therapy of Hyperthyroidism(Treatment of thyroid diseases)?


131
 1 is the agent of choice for treatment of thyroid conditions
a. I-131 emits beta particles that deposit 90% of their radiation energy within an area of less
than 1 mm from the decaying radiation atom.

b. Physical half life of 8 days (enough time to transport, enough time in stock)

c. easy, safe and simple treatment

d. I-131 emits gamma photon that can be measured by external radiation detectors.
32. Common Indication And Contraindication For Radio(131I ) therapy ?
Indications
 Benign Conditions

 Hyperthyroidism

 Graves’ disease
 toxic multinodular goiter
 toxic autonomously functioning thyroid nodules
 Nontoxic goiter

 Well Differetiated Thyroid Cancer

 In treatment of well differentiated thyroid carcinoma, 1311 is used to


 postoperative ablation of thyroid remnants

 to treat recurrent thyroid cancer and metastatic disease

Contraindications
 Pregnancy
 Radioiodine freely crosses the placenta. The fetal thyroid concentrates iodine
after the 12th week and the radiation will destroy the thyroid gland and result
in severe hypothyroidism.
 activity in the maternal bladder causes significant fetal irradiation.
 it is recommended that conception be delayed for half/1 year after low/ high-
dose I-131 therapy.
 Breast feeding
 radioiodine are excreted in breast milk .
 Not resumed until next pregnancy.

[Link] are the Benefits of I-131 Therapy in well differentiated thyroid cancer ?

 Ablate residual microscopic malignancy and tissue destined to become malignant

 Destroy the normal thyroid tissue to optimize ablative radioiodide therapy for residual
or metastatic disease

 Eliminates the thyroid gland as source of thyroglobulin to facilitate the follow-up for
patients

 Decreases local recurrence or distant metastases

 Improves survival in patients following local recurrence or distant metastases.


[Link] are radiopharmaceuticals & radionuclides used in the the palliative treatments of
painful bone metastases?
The radiopharmaceuticals used for palliation of metastatic bone pain:
 Phosphate-32.
 Strontium-89.
 Samarium-153.
 Rhenium-186.

Most common radionuclides used:

89SrCl2, 153Sm-EDTMP

[Link] the Pain Flare phenomenon?

 In some patients, transient worsening of bone pain may occur within several
days (most often within 3d ) of injection and last several days (2–5 d).
 “Pain Flare” can be treated by increasing doses of analgesia, if required.
 flare phenomena are associated with good clinical response

[Link] are common indication and Contraindications of Palliative of Painful


Bone Metastases?

 The best candidates for radionuclide palliative therapy

1. patients with advanced cancer who have more than one bone metastatic lesion
and are not candidates for, or are refractory to, conventional analgesic medical
treatments.

2. The abnormal bone scan indicates increased osteoblastic activity.

3. Patients should have an estimated life expectancy of at least 3 months.

4. platelet count > 60G/L

leukocyte count > 3.0G/L

hemoglobin count > 100g/L

absolute granulocyte count > 2.0G/L

Contraindications

1. Patients with pain from other causes

2. Patients with absolute granulocyte count < 1.5G/L,


platelet count < 60G/L, hemoglobin < 90 g /L
3. 6 weeks before or following myelosuppressive chemotherapy

4. Pregnant patients are not candidates for therapy

5. Patients with impending spinal cord compression or impending long


bone fractures as evidenced by greater than 50% cortical erosion

6. Patients with severe renal failure (GFR less than 30 mL/min)


[Link] is SPECT ?
Stands for single-photon emission computed tomography,based on gamma camera
Consists of detector,gantry,computer and image reconstruction software, Produces three-dimensional
cross-sectional images. The detector can rotate over 180 degrees or 360 degrees.

38. PET Annihilation Radiation?

When a positron travels a distance in the incident direction, aka range (R), it loses all its energy
at the end of its range, and combines with an electron and annihilates. The mass energy of the
electron and the positron is converted into two γ-rays of 511keV that travel in opposite
directions.
Chapter1
What Is Nuclear Medicine?
A branch of medicine is concerned with the use of radioactive materials in the diagnosis and
treatment of disease and medical research.

Nuclear medicine imaging provides information about both structure and function.
category:
basic nuclear medicine
clinical nuclear medicine
Content:
Radionuclide imaging
Function evaluation
Radionuclide therapy
In vitro methods (radioimmunoassay)

The history of nuclear medicine


1895 Wilhelm Roentgen →x ray
1896 Henri Becquerel →uranium --x ray
1898 Marie Curie → radium / polonium
1901 Wilhelm Roentgen → Nobel Prize (physics)
1903 Curie / Becquerel →Nobel Prize (physics)
1911 Curie →Nobel Prize (chemistry)

SPECT ——single photon emission computed tomography


PET ——positron emission tomography

nuclide
A nuclide is any individual atomic species, characterized by a specific number of protons , neutrons
and energy state.

isotope
The isotopes of an element are having the same protons but different neutrons.
Isotopes have similar chemical properties.
1H 2H 3H
13153I 12553I 12353I

isomer
Isomers are nuclides having the same number of protons and neutrons , but different energy state.
An atom is radioactive (unstable) if these forces among the particles that make up the nucleus are
unbalanced.
An atom is radioactive (unstable) if these forces among the particles that make up the nucleus are
unbalanced.

radionuclide: it refers to the unstable nuclei spontaneously emit radiation (such as alpha, beta ray)
to form another nuclei or nuclear energy state by decay.

(Radiation )decay
The process by which an atomic nucleus of a radionuclide spontaneously emits radiation and
simultaneously transforms into another nucleus

Radiation decay
Alpha (α) decay
Beta-minus decay
Beta-plus decay
Electron capture
Gamma (γ) decay
Alpha (α) decay
Heavy nuclei tend to be unstable because they contain large numbers of protons that strongly repel
each other.
Alpha(α) decay
The alpha particle consists of :
two protons and two neutrons,
being identical to a 42He nucleus without the orbiting electrons:
AZX → A-4Z-2Y + 42He +Q(Decay energy)

Beta-minus decay
A nucleus that has too many neutrons for stability cannot simply emit a neutron

Beta-minus decay
The antineutrino is the antiparticle of an elusive entity called the neutrino.
AZX → AZ+1Y + βˉ + υˉ + Q

Beta-plus decay
a proton is transformed into a neutron with the emission of a positron(e+ )and a neutrino(υ)
Proton →Neutron + Positron + Neutrino
AZX → AZ-1Y + e+ + υ

Electron capture
It is an alternative to beta-plus decay, electron capture, that accomplishes the same result.
Proton + Orbiting electron → Neutron + Neutrino

The emission of characteristic X rays dominates in high-Z materials.

The expulsion of an electron is much more likely in low-Z elements ( Auger electrons)
Internal conversion
When a nucleus shifts from a high-energy state to a low-energy state , the excess energy is transmitted
directly to electrons , it can send electrons out.

Gamma decay
A nucleus in an excited condition will eventually return to the ground state .

The movement of nucleons to lower energy orbits typically gives rise to the emission of photons
called gamma rays.

Often, when a radionuclide decays, the decay product is radioactive , too.


go through many steps decay.

How long do radionuclides stay radioactivity?


It depends on the type of radioactive materials.
The rate of decay is one of the characteristics of radionuclides.

half-life
T1/2 : the half-life of the radionuclide.
a time period that the number of nuclei decrease by one-half.

Interaction of charged particles with matter


Ionization
Excitation
Scattering
Bremsstrahlung
Absorption
Cherenkov radiation
Ionization

It refers to the process of forming free electrons and positive ions by the electrostatic interaction
between the charged particles and the outer electrons of the material atoms.
Interaction of charged particles with matter
Excitation

When charged particles pass through the material, the energy obtained by the nuclear electron is not
enough to make it out of the atom, but only from the inner layer to the outer layer.
the atoms become excited states from the steady states.
Interaction of charged particles with matter
Scattering
After the collision between the charged particles (Beta ray) and the nucleus of the material, the
movement direction and the energy of the particles are changed.
Interaction of charged particles with matter
Bremsstrahlung

Fast electrons pass through the material, under the action of electric field in atomic nucleus, the
direction of motion is changed, and the speed is reduced dramatically, a part or all of the electron
energy is converted into a continuous energy by the X - ray emission.
Interaction of charged particles with matter
Absorption

In the process of ionization and excitation of the atoms in the material by the charged particles, the
energy of the rays is completely depleted, and the rays are no longer in existence.
Interaction of charged particles with matter
Cherenkov radiation
When velocity of charged particles in the medium is greater than the speed of light, they will emit a
faint with short wavelength based radiation, called Cherenkov radiation.

Interaction of photons with matter


Photoelectric effect
A photon interacts with the atom, losing all its energy in the process.
An inner shell electron (usually a K shell electron) is ejected from the atom, leaving a vacancy in the
inner shell.
When the vacancy is filled by another electron, photons (characteristic X rays) will be emitted.

Compton effect( Compton scattering)


To "scatter" means to change direction.
A photon interacts with an outer shell electron in an atom of the material that the photon is traversing.

The photon changes direction after meeting the electron, the electron is knocked away from the atom,
and the photon loses whatever energy the electron acquires .

Pair production
A photon interacts, not with the atomic electrons, but with the electric field of the nucleus. In the
process the energy of the photon is converted into mass, an electron and positron pair can be
produced .

Radiation protection

Irradiation
The international system of units :C · kg -1
The old private units : R, mR μR。
1 R = 2.58×10 -4 C · kg -1
Absorbed dose
The unit of absorbed dose
The international system of units : Gy
The old private unit : rad

dose equivalent( H) :
The unit of dose equivalent
The international system of units : Sv

Radiation effects
International Commission of Radiation Protection (ICRP) :
determinate effects;
stochastic effects
Determinate effects
The severity of the effect varies with the dose and the effects are not seen below a certain threshold
level of radiation.

Stochastic Effects
These effects have no threshold and the severity of the effect does not vary with the dose.

The probability of occurrence, however, increases as the dose increases.


Stochastic Effects
Cancer is a stochastic effect, particularly leukemia which has a latent period of 2 to 10 years post
exposure.
The risk for leukemia is significantly increased above acute doses of 40 rads (0.4 Gy).

Genetic effects, Mutagenesis


Principles of radiation protection
Justification
Optimization
Individual dose and risk limitation

Justification:
No practice involving exposures to radiation should be adopted unless it produces enough benefit
to the exposed individuals or to society to offset the radiation detriment it causes.

Optimization:
Exposures to radiation should be as low as reasonably achievable.

Individual dose and risk limitation:


No individual should receive radiation doses higher than the maximum allowable limits.
Radiation Workers
Whole Body: accumulative equivalent dose less than 100mSv in continuous 5 years,
and less than 50mSv among any year.

Lens: 150mSv
Skin: 500mSv
Other organs: 500mSv
Non-radiation worker
Accumulative yearly equivalent dose less than 1mSv,
or yearly average dose less than 1mSv in continuous 5 years
(not including patients who received diagnostic or therapeutic radiopharmaceuticals) .
External radiation protection measures
Time
Distance
Shielding
Time
The amount of radiation exposure increases or decreases with the time people spend near the source of
radiation.
Gamma and x-rays are the primary concern for external exposure.
Distance
As a rule, if you double the distance, you reduce the exposure by a factor of four.
Halving the distance, increases the exposure by a factor of four.

Shielding
The greater the shielding around a radiation source, the smaller the exposure.
The amount of shielding required to protect against different kinds of radiation depends on how much
energy they have.

Chapter 2 radiopharmaceutical

A radiopharmaceutical is a radioactive compound used for the diagnosis and therapeutic treatment of
human diseases. A radiopharmaceutical has two components: a radionuclide and a pharmaceutical.

Components of radiopharmaceuticals
• radionuclides
• non radioactive labeled substances
Main features of radiopharmaceuticals
• 1. Radioactive
• 2. Instable
• 3. Self radiation decomposition
• 4. Few amount
Cyclotron
Equipment in which charged particles, after acceleration in a circular pathway, are directed onto a
target for evoking a nuclear reaction.
Generator
A device in which a daughter radionuclide with a shorter half-life is separated from a mother
radionuclide with a longer half-life.
Half-life
The characteristic of a radionuclide that defines the time during which the radioactivity of a
radionuclide is reduced to half of its original value.
Radionuclidic purity
Fraction of the total radioactivity present as the desired radionuclide.
SPECT
Single-photon emission computed tomography: an imaging technique that makes use of a
radiopharmaceutical that is labelled with a gamma emitter.
. Radionuclide generator
The generator is a device for the production of radionuclides, which can produce regularly the
daughter radionuclides by decay from the radioactive parent nucleus. The parent radionuclide half-life
is long, the half-life of the daughter radionuclide is generally short, and the nuclear generator is often
called the "cow".
Ideal radiopharmaceutical
• Easy availability
• Short effective half-life
• Particle emission
• Suitable energy
High target-to-nontarget activity ratio

Chapter 3 instrumentation
Nuclear medicine instrumentation means some special systems, which measure and detect the amount
of ionizations or excitation events. [radiation (types, energy, radioactivity, changing regulations with
time and space distribution of radionuclides)]

Gamma counters are radiation detection systems used to monitor radionuclide that emits low energy
gamma radiation (51Cr,125I).
scintillation detectors;
Scintillator
Photomultiplier Tube
Preamplifier and main amplifier
Ionizatinng detector: ion chamber; Geiger-Mueller tubes;

Chapter 4 Nuclear Endocrinology

Most commonly used isotopes in thyroid


▪ 131I, Radioiodine-131
▪ 123I, Radioiodine-123
▪ 99Tcm , Technetium-99m
131
▪ I
▪ delivers both beta and gamma radiation
▪ gamma energy is 364 keV
▪ half-life is 8 days
▪ used for
▪ Thyroid uptake test
▪ Thyroid imaging
▪ Therapy
▪ 99Tcm (99Tcm O4-)
▪ pure gamma emitter
▪ energy 140 keV
▪ half-life 6 hours
▪ it is not organified, after trapping it is relatively quickly released back to the blood
▪ Used for imaging only
▪ The ability of thyroid iodine uptake reflects the metabolism status of thyroid gland
▪ High radioiodine uptake reflects hyperactive metabolism
▪ Low uptake reflects hypoactive metabolism
▪ Radioactive iodide uptake (RAIU) is the percentage of administered radioiodine incorporated
by the thyroid gland.
▪ Increased I-131 Uptake
Diseases
▪ Graves’ Disease
▪ Toxic multinodular goitre
▪ Solitary hyperfunctioning nodule
Other situations
▪ iodine deficient
▪ Rebound after withdraw of ATD/TH
▪ Decreased I-131 Uptake
Diseases
▪ Hypothyroidism: Primary or Secondary, Surgical/Radioiodine Ablation of Thyroid
▪ Thyroiditis: Acute, Subacute and Chronic Lymphocytic
▪ Renal failure, congestive heart failure: increased iodide retention
Other situations
▪ Iodine overload(medicine, food)
▪ Thyroid hormone
▪ Anti thyroid drugs
▪ Adrenal cortex hormone
▪ Clinical indications
Thyroid uptake measurements can be made for the following reasons
▪ To determine the functional status of the thyroid gland
▪ To calculate specific doses of 131I for the treatment of hyperthyroidism
▪ To differentiate subacute or painless thyroiditis and factitious hyperthyroidism from
Graves’ disease
▪ Perchlorate Discharge Test
This test is used to identify congenital or acquired organification defects which most commonly
involves the enzyme iodide peroxidase.

Thyroid Scintigraphy
▪ Radioactive imaging agent
▪ Thyroid Uptake / γ-ray
▪ Most common: 123I, 131I, 99TcmO4-
▪ Others: 18F-FDG, 99Tcm-MIBI
Clinical indications
▪ Thyroid scintigraphy may be required for any of the following purposes:
▪ To determine the size of the thyroid gland;
▪ For localization of thyroid nodules;
▪ To determine the activity of thyroid nodules;
▪ To determine functional status of the thyroid gland;
▪ To evaluate presence of ectopic thyroid tissues, thyroglossal duct cysts and substernal
masses.
Clinical Application
1. Localization of Ectopic Thyroid Gland
2. Determination of Nodule Function
3. Differentiate Diagnosis of benign from malignant
4. Differentiate Diagnosis of neck mass
5. Detection of thyroid cancer metastasis
6. Evaluation of thyroid weight
131
I whole body scan, Clinical applications :
1. Evaluation of remnant thyroid tissue post surgery in DTC
2. Decision about the extent of metastatic DTC
3. Correct staging of DTC
4. Assessment of the response to therapy in DTC
Chapter 5 skeletal system
main advantages
 An imaging can show the whole body bone;
 Compared with the radiological examination(X ray or CT), the lesions are found earlier and
more in number
 High sensitivity;
major disadvantages
1. Low specificity
[Link] of fine anatomical structure
Metastasis lesions in bone are found by bone imaging 3 to 6 months earlier than those by X-ray
examination.
Ideal bone imaging agent
 1. good bone affinity.
 2. The imaging agent in the blood is cleared quickly, the target organ / background ratio is
high.
 3. the effective half-life is short, the absorption dose of the human body is low.
 4. radionuclides for gamma rays, moderate energy.
Bone imaging agent
(1) 99mTc-MDP
rapid blood clearance
target / non target ratio is high
an ideal imaging agent
(2) 99mTc-PYP
acute myocardial infarction of the positive imaging.
bone dynamic imaging
 After injection of imaging agents , continuous dynamic collection is carried out at different
time,
 Images of blood flow in the local bone and surrounding tissue, image of the blood pool and
delayed static bone imaging,
 It be divided into blood flow, blood pool phase, delayed phase.
Normal image
 The bone structure of the whole body is clear, and the radioactive distribution is symmetrical.
 Usually the radioactivity of dense bones or bone (such as limbs) backbone is lower, and the
development of loose bone and flat bone( such as skull, ribs, vertebrae, pelvis and long
bones of the epiphyseal end) is relatively concentrated.
 kidneys and bladder are developed.
The normal children, adolescents and adults have differences in bone imaging.
 The epiphysis of children and adolescents are generally concentrated imaging agents, they are
most obvious in the epiphyseal region, because normal epiphyseal growth centers and
regenerated bones can uptake more imaging agents
Doughnut sign
 It is a common abnormal signs of bone imaging, the center of the lesion is a radioactive defect,
and it is surrounded by radioactive concentration.
Super bone imaging
 The uptake of radioactive imaging agents is increased in the whole body bone , which is
common and uniform. The development of whole body bone is abnormal concentration , the
double kidneys are usually not developed, the radioactivity of soft tissue is very low.
The mechanism may be related to diffuse reactive bone formation.
 hyperparathyroidism : often involving the whole body bone.
 Malignant tumor metastasis: often involving axial bone and pelvis, with uneven distribution
of radioactivity or concentration range.
Influence factors of bone imaging
 1 drinking water
Patients drinking more water can reduce the blood tissue background radioactivity counts.
 2 renal function
Decreased renal function can also lead to decreased renal clearance.
 3 quality of imaging agents
The labeling rate of bone imaging agent should be above 95%,Otherwise the image is not
clear, the result of the judgment is affected
 4 scattering material
Ascites, obesity and breast enlargement can increase the distance between the target organ
and the detector. Tissue absorption of photons is also increased, thereby reducing the quality
of bone imaging.
 5 systemic treatment
Chemotherapy, radiotherapy and hormone therapy can change the biological distribution of
imaging agent. Bone uptake rate is decreased.
 6 artifact
Patient's clothes and body surface skin are polluted by urine. Patients who change their body
position or have metal foreign body, metal belt etc during the examination process .
Notice
 1, imaging agent injection site is often a radioactive hotspots. So the injection point should be
far away from the site of suspected bone lesions and should be marked, so as not to be
confused.
 2, Before imaging ,the patients should drink more water, and reduce the radioactivity of the
bladder through urination.
 3, urine pollution may also cause false radioactive hotspots. Therefore, the patients should be
instructed not to contaminate skin and clothing with urine.
 4, Check the patient before imaging, remove any metal accessories (belt, necklace).
clinical application
 (1) metastatic bone tumor
 (2) primary bone tumor
 (3) osteomyelitis
 (4) bone trauma
 (5) ischemic bone necrosis
 (6) metabolic bone disease
 (7) joint disease
 (8) bone graft

Chapter 6 Genitourinary System

Advantages of renal scintigraphy


1 radiation exposure
2 non-invasive
3 easily reproduced
4 no urine collection necessary
5 can be performed on an out-patient basis
6 Few adverse effects reported.
Common indications
 Determination of kidney function
 Diagnosis of renovascular hypertension
 Evaluation of renal transplant
 Diagnosis of urinary obstruction
 Differential diagnosis of intrarenal space occupying lesion
Radiopharmaceuticals
1 Glomerular filtration:
99m ,
Tc-DTPA(Diethylenetraminepentacetic Acid) 99mTc-TTHA,
99m
Tc-PAHIDA ,etc
2 Renal tubular epithelial secretion:
131
I-OIH, 99mTc-EC, 99mTc-MAG3,(Mercaptoacetyltriglycine) 99mTc-DADS, 99mTc-CO2-DADS, etc.)

Analysis
3 phases of normal renogram
 phase a(arrival of tracer)
 phase b(concentration)
 phase c(elimination)
Quantitive analysis
 peak time(tb)<4.5min
 half time(C1/2)<8min
 15min residue rate<50%
 difference between peak time<1min
 difference between peak value<30%
Seven types of abnormal curve
1.1 Parabola type
The curve rises slowly,gradually falls and Tmax [Link] suggests the patients suffer from
mild renal insufficiency.
1.2 Low level prolonged type
Height of phase a is lowered ,while phase b and c merged each [Link] indicates severe renal
injury.
1.3 Low level descending type
The curve shows significant low phase a with gradual down slope ,without phase b and
[Link] patients usually have nonfuntional kidney,representing blood background activity only .
1.4 Acute rising type
Phase a is normal, phase b is continued uprising,but phase c is [Link] this condition,it
means
urinary obstruction.
1.5 High level prolonged type
Phase a is normal too,and phase b rises [Link] curve always occurs in urinary
obstruction with renal insufficiency.
1.6 Stepwise drop type
Phase a and b are normal,but phase c drops step by [Link] is seen in spasmodic ureter.
1.7 Small kidney type
The curve is very similar to the normal one,but the height of curve is much lower than normal
[Link] presents congenital small kidney or renal failure pattern.
Evaluation
The renogram is very useful.
1)It can screen for the diagnosis of renovascual hypertension
2)Investigate obstructive uropathy such as acute and renal stone
3)Diagnose acute anuria
4) Monitor the therapeutic effect of renal disease
5)Monitor renal function in renal transplant.
Glomerular Filtration
 Glomerular filtration rate(GFR):
The plasma volume(ml) filtrated through the glomerulus per minute
Normal value: 80-100 ml/min
Increase: In early stage of diabetes.
Decrease: Renal insufficiency, in the late stage of diabetes,the 3rd stage of hypertension,
azotemia,uremia
Effective Renal Plasma Flow( ERPF):
Clearance of the plasma volum(ml) per minute during the first pass of the injected material
through the kidney .
Common indications
Clinical application
 Determination of kidney function
 Diagnosis of renovascular hypertension
 Evaluation of renal transplant
 Diagnosis of urinary obstruction
 Differential diagnosis of intrarenal space occupying lesion

Chapter 7 oncology

 What is PET ? What are the basic principles of FDG PET imaging?
 PET is short for Positron Emission Tomography. PET is a nuclear medicine imaging
technique which produces a three-dimensional image or picture of functional process in the
body. The system detects pairs of 511 keV gamma rays emitted indirectly by
a positron-emitting radionuclide (tracer), which is introduced into the body on a biologically
active molecule. Three-dimensional images of tracer concentration within the body are then
constructed by computer analysis.
 What are indications for 18F-FDG PET/CT ?
 A. Differentiating benign from malignant lesions
 B. Searching for an unknown primary tumor
 C. Staging known malignancies
 D. Monitoring the effect of therapy on known malignancies
 E. Determining whether residual abnormalities represent tumor or posttreatment fibrosis
or necrosis
 F. Detecting tumor recurrence, especially in the presence of elevated levels of tumor
markers
 G. Selecting the region of a tumor most likely to yield diagnostic information for biopsy
 H. Guiding radiation therapy planning
 I. Nononcologic applications, such as evaluation of infection and atherosclerosis.
 What is the cause of PET Image artifacts ?
 1. Patient motion; respiratory motion
 2. Displacement of organs and bowel by bladder or rectal filling
 3. IV contrast and Oral contrast (barium )
 4. Metallic hardware: Metal implants associated with chemotherapy ports, artificial joints,
or dental fillings ,
 5. Cardiac pacers
 6. Subcutaneous infiltration of the tracer

 Positrons and annihilation radiation are the basis of PET imaging in physics.
 • Coincidence events in PET can be of four kinds: true, scattered, random and multiple.
 •
 True coincidence: Both photons from an annihilation event are detected by detectors in
coincidence. Neither photon undergoes any form of interaction prior to detection, and no
other event is detected within the coincidence time-window.
 Scattered coincide

 SUV (Standardized Uptake Value)???
 Generally, SUV values of 2.5 or greater have been used in differentiating benign from
malignant lesions as reported.

Chapter 8 Cardiovascular Nuclear Medicine


Myocardial perfusion imaging(MPI)
Radiopharmceuticals
Single photon tracers of MPI
 Tracers:201Tlcl,99mTc-MIBI,99mTc-tetrofosmin,99mTc-teboroxime
 Scanner:SPECT, SPECT/CT
 Principle:variant
 Characteristic:re-distribution (201Tlcl)
PET tracers
 Tracers:82Rb, 13N-NH3
 Scanner: PET, PET/CT
Tomography
Short Axial:from apical → bottom (Basal),
showed anterior wall, septum, inferior wall and lateral wall.
Vertical Long Axial:from interval → to Lateral,
showed anterior wall, apex, inferior wall and posterior wall.
Horizontal long axial:from septal → to anterior,
showed lateral wall, septum and apex.

Abnormal Image
 Reversible defect:myocardial ischemia
 Fixed defect:myocardial infarction or scar tissue or severe myocardial ischemia
 Mixed defect:myocardial ischemia and myocardial infarction
 Tinea sample change :cardiomyopathy or myocarditis
 Reverse redistribution :unknown reason
Clinical Applications
1. Diagnosis, risk stratification and outcome evaluation of CAD
2. Evaluation of myocardial viability
3. Evaluation of myocardial infarction
4. Evaluation of intermediate lesions
5. Assessment of treatment of PCI or CABG
6. Prediction of heart events before no-heart surgery
7. Diagnosis of cardiomyopathy or myocarditis

Myocardial Metabolic Imaging


 Glucose metabolism
 Aerobic metabolism
 Lack of oxygen metabolism
 Fatty acids metabolism
 Amino acids metabolism
Radiopharmaceutical: 18F-FDG
Instruments: PET, PET/CT
Clinical Application
Evaluation of myocardial viability

Chapter 9 Central Nervous System


Principle
 The brain receives 20% of the cardiac output, its weight is only 2% of body.
 The brain relies on continuous blood flow to supply needed.
 This regulation is relatively independent of the systemic circulation and is determined by
regional cerebral function and metabolism.
 The ‘trinity’ of metabolism–function–blood-flow of the brain.
 SPECT studies of brain perfusion using 99mTc labelled radiopharmaceuticals.
 Reflect the regional cerebral blood flow (RCBF) distribution in different areas.
 The tracers used must be able to cross the BBB.
 Radiopharmaceuticals with basic properties
 Lipophilia,
 Electrically neutral,
 Small molecule
 They can remain fixed in the brain long enough to be imaged by loss the lipophilicity.
Radiopharmaceuticals
All are highly lipophylic agents freely able to cross the intact BBB
 HMPAO(Technetium-99m-hexamethyl propylamine oxime)
 Convert to a hydrophilic form unable to recross the BBB
 ECD (Technetium-99m-bicisate ethyl cysteinate dimer)
 Retained because of hydrolysis of its ester group
 IMP (I-123-isopropyliodoamphetamine)
 Probably combined to some receptor site in the brain
Clinical Indications
 Detection and evaluation of cerebrovascular disease
Stroke
Transient ischemic attacks(TIA)
Subarachnoid hemorrhage(SAH)
Arteriovenous malformation(AVM)
Other derangements of cerebral hemodynamics
 Management of a patient with epilepsy
 Evaluation of patients with suspected dementia
 Evaluation of brain tumor
 Anxiety disorders and affective disorders
 Addictions
 Management of patients with schizophrenia
 Management of patients with movement disorders

Chapter 10 Radionuclide Therapy


What is radionuclide therapy?
 It uses radiation from the decay of radionuclides to treat diseases.
 mainly includes:
 [Link] targeted therapy (radio immunotherapy)
 [Link] interventional therapy (radioactive seed implantation therapy)
 [Link] application(敷贴)therapy
principle of radionuclide therapy
 Radiopharmaceuticals can be delivered to diseased tissues or cells by carriers or
interventional pathways. Or the tissues or cells can actively ingest the drugs. A large number
of them are concentrated in the lesion sites.
 Radiation emitted by radionuclides decay acts on biological macromolecules (such as
nucleic acid and protein), by breaking up their chemical bonds to change molecular structure
and function, then inhibit or kill diseased cells.
Commonly used Radioactive particles
1. alpha particles
2. beta particles
3. Auger electrons
Beta-Emitting Radionuclides
 iodine-131 , yttrium-90, samarium-153, strontium-89
Alpha-Emitting Radionuclides
 bismuth-213,astatine-211,radium-223
Auger Electron-Emitting Radionuclides
 bromine-77, indium-111,iodine-123, iodine-125
 Radiopharmaceuticals Application
 Iodine-131(NaI) Graves’ Disease,Thyroid Cancer
 32phosphorus sodium phosphate 磷酸钠 Polycythemia(红血球增多症)
 89Strontium (SrCl2) Bone metastases
 153Samarium-EDTMP Bone metastases

 1311 is the agent of choice for treatment of thyroid conditions


131
a. I emits beta particles that deposit 90% of their radiation energy within an area of less than 1
mm from the decaying radiation atom.
b. Physical half life of 8.04days (enough time to transport, enough time in stock)
c. easy, safe and simple treatment
d. 131I emits gamma photon that can be measured by external radiation detectors.
 Therapy means the oral administration of 131I as sodium iodide to patient in fasting state.

Common indication
 Benign Conditions
 Hyperthyroidism
• Graves’ disease
• toxic multinodular goiter
• toxic autonomously functioning thyroid nodules
 Nontoxic goiter
 Well Differetiated Thyroid Cancer (WDTC)
Nuclear medicine
review
Terms & concepts:
1. Nuclear medicine : a branch of medicine concerned with use of radioactive materials in the
diagnosis and treatment of disease ( include using radiation as therapy , radiopharmaceuticals
to diagnose disease ,etc. )
2. T1/2 : the half life of the radionuclide , a time period that the number of nuclei decreases by
one half . (1/teff=1/tp+1/tb )
3. Radioactivity : the size or weight of a quantity of material does not indicate how much
radioactivity is present . radioactivity is measured in units of Becquerel (Bq).
4. Bq : 1 event of radiation emission per second. ( 1 Ci= 3.7x10^ 10 Bq )
5. Determinate effects : the severity of the effect varies with the dose and the effects are not
seen below a certain threshold level of radiation.
6. Stochastic effects : these effects have no threshold and the severity of the effect dose not vary
with the dose. The probability of occurrence , however , increases as the dose increases .
7. PET ( positron emission tomography) : is the innovative medical imaging technology for
detection of cancer, brain disorders, and heart disease. PET provides quantitative biochemical
information such as metabolism, blood flow, blood volume . can find disorders earlier and
more accurate than CT/MRI.
8. SUV: mean selected region activity. [ (mCi/ml)/{injected dose(mCi)/body weight(kg)} ]
9. Luxury perfusion : Abnormal hyperperfusion around the infarct foci.
10. Crossed diaschisis : When one side cerebrum cortex has low or defect radioactivity areas, the
other side cerebrum or cerebellum has foci, too.
11. Reversible defect:myocardial ischemia
12. Mixed defect:myocardial ischemia and myocardial infarction
13. Fixed defect:myocardial infarction or scar tissue or severe myocardial ischemia
14. Tinea sample change :cardiomyopathy or myocarditis
15. reverse redistribution :unknown reason

16. Perchlorate Discharge Test : Indicate the presence of an defect of iodide organification

Questions :
1-Character of nuclear medicine ?
-specialists use safe, painless, and cost-effective techniques to image the body and
treat disease
-is unique, because it provides doctors with information about both structure and
function.
-procedures often identify abnormalities very early more than other diagnostic tests.

2-is nuclear medicine safe ?

-it uses very small amounts of radioactive materials to diagnose and treat disease.

-in imaging the radiopharmaceuticals are detected by special type of nuclear medicine
instrumentation that work with computers to provide very precise pictures about the area of the body
being imaged.

-in treatment the radiopharmaceuticals go directly to destroy the tumor cell.

- the amount of radiation in the typical nuclear imaging procedure is the same as a diagnostic X-ray,
and the amount received in a typical treatment procedure is kept within safe limits .

3- clinical application of MPI ?

• The main part of Nuclear Cardiology, Take an important role in the detection and
management of coronary artery disease appearance of images of MPI:

radioactivity normal normal distribution of blood flow

(no obvious blood vessel lesion)

radioactivity decrease low blood flow

(significant blood vessel lesion)

radioactivity defect no blood flow(total occlusion)

4-comparsion between bone scan and radiography :

Methods Parameter of Time of Extension of Resolu- Specifi-


revealment visualization tion city
measurement

X-ray anatomy Changes of region better high


skeletal
Calcification
>30%
Bone blood flow, 3-6 months whole body worse low
scan metabolism earlier than bone
above

5- super scan ?
very high concentration in bones,
very little in soft tissues,
no images in both kidneys and bladder.

-Clinical significance:

Extensive bone metastasis of malignancy.

Hyperparathyroidism

6-analysis of renogram ?

 3 portions of normal renogram

– portion a(arrival of tracer)

– portion b(concentration)

– portion c(elimination)

 Quantitive analysis

– peak time(tb)<4.5min

– half time(C1/2)<8min

– 15min residue rate<50%

– difference between peak time<1min

– difference between peak value<30%

7-clinical application of renogram ?

 Diagnosis of urinary tract obstruction

 Determination of each renal function

 Determination of renovascular hypertension

 Monitering kidney transplantation.


 Others.

8- Radiopharmaceuticals of renogram (renal dynamic imaging ) ?

 Glomerular filtration: 99mTc-DTPA, 99mTc-TTHA, 99mTc-PAHIDA etc.

 Renal tubular epithelial secretion: 131I-OIH, 99mTc-EC, 99mTc-MAG3, 99mTc-DADS, 99mTc-CO2-DADS,


etc.

9- Clinical indications of RAIU Test (Radioactive iodide uptake test ):

-To determine the functional status of the thyroid gland

-To calculate specific doses for the treatment of hyperthyroidism

-To Differentiate subacute or painless thyroiditis and factitious hyperthyroidism from Graves’ disease

10- Radiopharmaceuticals and clinical application of Thyroid Scintigraphy ?

Radiopharmaceuticals :

 Most common: 99TcmO4- , 123I, 131I,

 Tumor positive: 18F-FDG, 99Tcm-MIBI, 201Tl

Clinical Application of thyroid scintigraphy

 Localization of Ectopic Thyroid Gland

 Determination of Nodule Function

 Differentiate Diagnosis of benign from malignant

 Differentiate Diagnosis of neck mass

 Detection of thyroid cancer metastasis

 Evaluation of thyroid weight

11- Parathyroid Scintigraphy Methods and clinical application ?

Methods:

 Subtraction imaging

 Dual-phase imaging

Clinical Application :
 localizing of the hyperfunctioning parathyroid gland (adenoma or hyperplasia) before
surgery for shortening operation time

12- adrenal gland imaging : cortex and medulla imaging

Adrenal Cortex Imaging Adrenal Medulla Imaging

131 123 131


Radiopharm I-6-IC I-/ I-MIBG

Clinical study of adrenocortical localizing Pheochromocytoma, neuroblastoma,


Application hyperfunction carcinoids and medullary thyroid carcinomas

13- What is Radionuclide therapy and which radiation could be used in it?

is a form of radiotherapy useing unsealed radionuclide as radiation sources for the selective delivery
of radiation to tumours or target organs. By virtue of ionizing properties of radiation, radionuclide
achieves its therapeutic purposes.

-radiation used

There are three types of particulate radiation of consequence for targeted radionuclide therapy—beta
particles, alpha particles, and Auger electrons—which can irradiate tissue volumes with multicellular,
cellular and subcellular dimensions,respectively.

14- Treatment of Thyroid Diseases

-The agent of choice for treatment of thyroid disease is 1311


-131
1 could be used to treat :

a- Thyroid benign conditions, include

b- Graves’ disease, toxic multinodular goiter, toxic autonomously functioning nodules, and Nontoxic
goiter

c- And well differentiated thyroid carcinoma :

In treatment of well differentiated thyroid carcinoma, 1311 is used to


a- postoperative ablation of thyroid remnants

b- treat recurrent thyroid cancer and metastatic disease

15- Contraindications and benefits of 1311 therapy ?

Contraindications:

 pregnancy, breastfeeding

Benefits of I-131 Therapy in well differentiated thyroid cancer

 Ablate residual microscopic malignancy and tissue destined to become malignant

 Destroy the normal thyroid tissue to optimize ablative radioiodide therapy for
residual or metastatic disease

 Eliminates the thyroid gland as source of thyroglobulin to facilitate the follow-up for
patients

 Decreases local recurrence or distant metastases

 Improves survival in patients following local recurrence or distant metastases

16- Palliative Treatment of Painful Bone Metastases ?

-Most common radionuclides used


89
SrCl2, 153Sm-EDTMP

-Pain Flare : In some patients, transient worsening of bone pain may occur within several days (most
often within 3d ) of injection and last several days (2–5 d). can be treated by increasing doses of
analgesia, if required. flare phenomena are associated with good clinical response

- Common Indications:

1. patients with advanced cancer who have more than one bone metastatic lesion and
are not candidates for, or are refractory to, conventional analgesic medical
treatments.

2. The abnormal bone scan indicates increased osteoblastic activity

3. Patients should have an estimated life expectancy of at least 3 months

4. platelet count > 60G/L

leukocyte count > 3.0G/L

hemoglobin count > 100g/L


absolute granulocyte count > 2.0G/L

- Contraindications :
1. Patients with pain from other causes

2. Patients with absolute granulocyte count < 1.5G/L, platelet count < 60G/L,
hemoglobin < 90 g /L

3. 6 weeks before or following myelosuppressive chemotherapy

4. Pregnant patients are not candidates for therapy

5. Patients with impending spinal cord compression or impending long bone fractures as
evidenced by greater than 50% cortical erosion

6. Patients with severe renal failure (GFR less than 30 mL/min)

17- clinical indication of RCBF ?

18-what are the principles of radiation protection ?

A- justification: No practice involving exposures to radiation should be adopted unless it produces


enough benefit to the exposed individuals or to society to offset the radiation detriment it causes.

b- Optimization: Exposures to radiation should be as low as reasonably achievable.

c- Individual dose and risk limitation: No individual should receive radiation doses higher than the
maximum allowable limits.

19- what are the basics of external radiation protection ?

a- Time: The amount of radiation exposure increases and decreases with the time people spend near
the source of radiation.

b- Distance: As a rule, if you double the distance, you reduce the exposure by a factor of four.

c- Shielding : The greater the shielding around a radiation source, the smaller the exposure.

20- what is the cause of PET image artifacts ?

a- patient motion : respiratory motion

b- displacement of organs and bowel by bladder or rectal filling

c- IV contrast and oral contrast

d- metallic hardware

e- cardiac pacers
f- subcutaneous infiltration of the tracer

21- what are the factors affecting SUV measurement ?

 Plasma glucose levels


 The time after FDG injection
 Subcutaneous infiltration of the tracer
 Body weight or body surface area
 Size of the region of interest
 Resolution of the scanner
 Type of image reconstruction and attenuation correction
 Patient motion

22- what are indications for 18F-FDG PET/CT ?

A. Differentiating benign from malignant lesions


B. Searching for an unknown primary tumor
C. Staging known malignancies
D. Monitoring the effect of therapy on known malignancies
E. Determining whether residual abnormalities represent tumor or post treatment fibrosis or
necrosis
F. Detecting tumor recurrence, especially in the presence of elevated levels of tumor markers
G. Selecting the region of tumor most likely to yield diagnostic information for biopsy
H. Guiding radiation therapy planning
I. Non-oncologic applications, such as evaluation of infection and atherosclerosis.
Chapter 2
Nuclear medicine instrumentation

1
Definition
• Nuclear medicine instrumentation means
some special systems, which measure and
detect the amount of ionizations or
excitation events.

• Radiation(types,energy,radioactivity
changing regulations with time and space
distribution of radionuclides) 2
Nuclear medicine Instruments
• Imaging instruments:
– Gamma camera, SPECT,PET, SPECT/PET-CT/MRI

• Function measurement instruments


• Thyroid/kidney function/gamma probe

• In vitro/ex vivo sample analyzer


• Gamma counter, liquid scintillation counter, radioactivity calibrator

• Radiation protection survey meter


– Ion Chamber:
– Geiger-Mueller Tube:

3
History of the development of
imaging nuclear medicine instrument

1950 Well type scintillation counter


Scintillation scanner
1951

1957 Gamma camera

PET Scintillation scanner


SPECT SPECT/CT PET/MR
PET/CT
1974
1979
2012
2001

(From dose calculator to imaging instrument) 44


Content of nuclear medicine
instrumentation
• 1 Principle to Detect and Measure • 2.3 photosensitive material
the Radiation detector
– Ionization • 2.4 Semi-conductor detector:
– Scintillation
– Chemical Mechanism
(sensitization) • 3 Type
– Gamma Counter
• 2 Detector and electronic circuit – Liquid Scintillation Counter
– 2.1 Ionizing detector: Ion – Personnel Monitoring
Chamber, Geiger-Mueller Tube: • SPECT, SPECT-CT
– 2.2 Scintillation Detector • PET,PET-CT/MRI
• 1 Scintillator
• 2 lightguide
• [Link] Tube 5
• 3 Preamplifier
1. Principle to Detect and Measure
the Radiation

Ionization

Scintillation Chemical
Mechanism

6
1.1 Ionization
• Radiation cause ionization of materials.
• The number of ion pairs collected can be related to the
amount of radiation causing the ionization.
Ion chamber, Geiger-Muller counter.

7
1.2 Scintillation
• Scintillation is the production of light following
the movement of electrons from high energy
levels orbits to lower energy levels within an
absorbing material.

• The electrons have moved into higher energy


orbits by the process of excitation.

• The light released can be converted to an


electrical signal. 8
1.2 Scintillation
• The size of the electrical signal depends on the
number of electrons moved into higher energy
orbits and can therefore be related to the amount of
radiation causing the scintillation.

9
1.3 Chemical Mechanism
• Ionizing radiation reacts with photographic film
in the same way as visible light.
• exposure to radiation blackens the film.
• Autoradiography

10
[Link]
Radiation Detector and electronic circuit
– 2.1 scintillation detectors;
– 2.1.1 Scintillator
– 2.1.2 Photomultiplier Tube
– 2.1.3 Preamplifier and main amplifier
– Ionizatinng detector: ion chamber; Geiger-
Mueller tubes;
– semi- conductors and so on.

11
2.1 Scintillation Detector
Scintillators photomultiplier tube preamplifier

radiation → a light photons →a pulse of electrons → electric signal

12
2.1.1Scintillator

– Solid scintillator (crystal)


SPECT:70-90%NaI (Tl):photoelectrical effect(100%)
PET:BGO, LSO,LYSO crystal

– Liquid scintillator
– High/medium/low engergy

13
2.1.2 Photomultiplier Tube (PMT)
• Photomultiplier Tube takes a light photon from
the scintillator and converts it into a pulse of
electrons and amplifies the pulse of electrons into
a measurable electrons current.
a light photon →a pulse of electrons

cathode(-) 105 -108 anode(+)

14
200-400V
2.1.3 Preamplifier
• The output signal is shaped and matched by
a preamplifier to ensure that no signal
distortion is introduced from the PMT to the
main amplifier.
• Finally, the signal is sent through a pulse
height analyzer (PHA) as counts.
a pulse of electrons → electric signal
15
Photomultiplier Tube (PMT) array
lateral
PMTs array tightly, cover PMT type
crystal visual field
Spacial resolution

round

sexangle

square

FOV 3" PMTs 2" PMTs

16
Photomultiplier Tube (PMT)
• Photons convert electric
pulse
signal amplification by
dynode
electrons • overall gain about 106
dynode visible light

anode photocathode

17
PHA

Energy position Z
signal signal Y

X
X
. . . . . . .
0 0 0 0 0 0 0 0 0 0 0 0
PMT PMT ARRAY 0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0
NaI(Tl) 0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0
crystal 0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 01 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0
collimator Y 0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0

image display
18
Ideograph PHA

Energy position
signal signal
detector
X Y Z
. . . . . . .
PMT
PMT ARRAY

NaI(Tl)
crystal

collimator γ –ray

image display

19
2.2 Ionizatinng detector
1. Ion Chamber
•The ion chamber consists of a cylindrical
chamber containing air at atmospheric
pressure.
•The interaction of radiation with gas
results in the ion pairs consisting of a negative
ion (electron) and a positive ion.
20
2.2 Ionizatinng detector
• 2. Geiger-Mueller Tube

• If the voltage in an ionization system is


increased beyond a certain point, an effect
known as gas amplification occurs.

21
2.4 Semi-conduct detector

22
3 Type
• 3.1 Gamma Counter
• 3.2 Liquid Scintillation Counter
• 3.3 Personnel Monitoring

23
3.1Gamma Counter
• Gamma counters
are radiation
detection systems
used to monitor
radionuclide that
emits low energy
gamma radiation
(51Cr,125I).

24
3.2 Liquid Scintillation Counter
• Liquid scintillation counting is a
method of assaying a radioactive
sample by dissolving it in a chemical
solution called scintillation fluid or
cocktail.
• They are ideal for-counting
radionuclide that decays by alpha
and beta particle emission (3H,14C,32p)
and may also be used to measure
some gamma emitters (125I,5l Cr)
which emit Auger electrons as part of
their decay. 25
3.3 Personnel Monitoring
• There are different types
of integrated dose
monitors including :
--film badges
--thermoluminescent
dosimeters (TLD)

26
• Radionuclide Tomography Gamma camera,SPECT
• SPECT
– Instrumentation
– Image Acquisition
and PET
• Collimator Selection Orbit
• Arc of Acquisition, Angular Sampling, and
Matrix Size Imaging Time
• PET
• Patient Factors
– Instrumentation
– Image Reconstruction
• Gantry Size
• Spatial Domain
• Detector lMaterials
• Fourier Transformation and Frequency
Domain • Coincidence Detection
• Angular projection (view) • Spatial Resolution
• Projection Profile (Slice Profile) – Image Reconstruction
• Ray Sum • Attenuation correction
and Quantitative
• Nyquist Frequency Analysis
• Backprojection • PET-CT
• Filters • Comparison of PET and SPECT
• Reconstruction in the Frequency Domain • SPECT Camera Imaging of
• Other Reconstruction Techniques 511keV Positrons (SPECT-
• Attenuation Correction PET)
– Image Reformatting: Transaxial, Sagittal, Coronal
and Oblique Views
27
– QualityAssurance
Image Instruments
• --Gamma Camera
Tomography:Tomographic techniques have been developed for
both single photon and positron tomography.
--SPECT
--PET

28
Gamma (γ) Camera

1957, Hal Anger 29


collimator, Scintillator, PMT, Preamplifer, main
amplifier,X、Y position electronic circut, PHA,
computer 30
Collimator

Spatial resolution: hole size(small), thickness


Sensitivity:1MBq-counts/s: hole size, thickness
Energy range:150-350keV

31
Scintillator crystal

• NaI ;gamma ray


• Photoelectric effect rate: 100%
• Humidity and temperature

32
Gamma (γ) Camera

33
4 SPECT
• Detector , Gantry, Bed, Workstation

34
SPECT
Two-headed systems are the most common
commercially available SPECT systems. In
particular, two-headed systems that allow
flexibility in orientation between the heads have
become popular.

35
SPECT
• Multiple heads are desirable because they
allow more data to be collected in a given
period. Rotational SPECT is "photon poor”
compared with x-ray CT.

36
SPECT

Two configurations for dual-headed SPECT systems. 37


4 SPECT

• SPECT is able to visualize the function of the body.


• The type of molecule chosen depends on what
information is required.

38
4 SPECT
• SPECT is short for Single Photon Emission Computed
Tomography.
• SPECT can show both structure and founction.
• SPECT works by detecting the positions of radioactive
tracers.

39
4 SPECT
• If a rotating camera is around the patient, the
camera will acquire views of the tracer distribution
at a variety of angles. After all these angles have
been observed, it is possible to reconstruct a three
dimensional view of the radiotracer distribution
within the body.

40
4 SPECT
The components making up the SPECT are the
collimator, detector crystal, photomultiplier
tube array, position logic circuits, and the data
analysis computer, etc.

41
4.1Collimator
• The collimator is a pattern of holes through gamma
rays absorbing material, which usually is lead or
tungsten.
• The collimator achieves this by only allowing those
gamma rays traveling along certain directions to
reach the detector, this ensures that the position on
the detector accurately depicts the originating
location of the gamma ray.

42
4.1Collimator
• A Thallium-activated Sodium Iodide [NaI(TI)]
detector crystal is generally used.
• A detector crystal may be circular or rectangular. It is typically
3/8 inch thick and has dimensions of 30-50cm.

43
Crystal (NaI )
•high sensitivity for γ –ray
•Monoblock crystal (40 x 50 cm )

•Thickness:3/8,5/8 and 1 inch


g-ray convert visible light

•brittleness:sensitive for collision,

humidity and temperature

44
4.2 Reconstruction Algorithm
• The most common algorithm used in the
tomographic reconstruction of clinical data is the
filtered backprojection method and iterative
reconstruction methods.

45
4.2.1 Projection
• As a SPECT camera rotates around a patient, it creates
a series of planar images Called projections.
• After all the projections are acquired, they are
subdivided by taking all the projections for a single,
thin slice of the patient at a time.
• It represents the projection of the tracer distribution in
the body into a single slice on the camera at every angle
of the acquisition.

46
4.2.2 Backprojection
• As the original data are collected by only allowing
photons emitted perpendicular to the camera face to
enter the camera, backprojection smears the camera
bin data from the filtered sinogram back along the
same lines from where the photon is emitted from.
• Regions where backprojection lines from different
angles intersect represent areas which contain a higher
concentration of radiopharmaceutical.

47
Backprojection

48
4.2.3 Filtering
• Once the data have been transformed to
the frequency domain, the statistical noise
is then smoothed out by filters.
• Some typical filters used are :
– the Hanning filter,
– Butterworth filter,
– low pass cosine filter,
– Weiner filter, etc.

49
Filtered
Backprojection

50
4.2.4 Attenuation Correction

• Due to the influence of different anatomical


structures and densities of human tissues,
distorted images are obtained. The purpose
of attenuation correction is to get a more
realistic image.

51
SPECT Camera Imaging Of 511kev
Positrons (SPECT-PET)
• The feasibility of imaging positron-emitting
radionuclides with SPECT systems has been widely
explored.

• The use of this approach has been established with


greatest applicability to studies of the heart and certain
tumors using fluorine-18 (18F-FDG).
52
SPECT Camera Imaging Of 511kev
Positrons (SPECT-PET)
• Although initially imaged with very high
energy collimator, non-collimator
systems incorporating coincidence
detection circuitry have been developed
for and used with dual-headed SPECT
devices. Spatial resolution is considerably
better when coincidence detection is used.
These systems became commercially
available.

53
Fusion imaging by Hawkye

54
5 PET
• Positron Emission Tomography ,also called PET
imaging , is a nuclear medicine technology that uses
short-lived radionuclide attached to biological molecules
to allow the visualization of metabolic processes in the
body by producing an image of the distribution.

55
5 PET
• The commonly used positron emitted nucleus in PET
is 11 C, l3N, l5O and 18 F.
– 18F can be used to substitute hydrogen or hydroxyl
groups.

56
PET ring detector

57
58
5 PET
• The positron travels only a short
distance in tissue, then it γ
annihilates with an electron into
two 511keV gamma quanta or
photons, which are emitted back
to back. b-
• When these two gamma quanta b+
are detected by two detectors in
coincidence then the decay event
18F
can be localized to the line
connecting the two detectors.
This “electronic collimation”
allows constructing highly γ
efficient detection systems.

59
5 PET
• Commercial tomography consists of thousands of
detectors, which are arranged in many rings
surrounding the object.

• Each detector is connected in coincidence with


opposing detector.

60
5 PET
• The early tomography used NaI(T1)crystals as
scintillation detectors.
• These were soon substituted by BGO (bismuth germanate) crystals,
which have higher detection efficiency and are not hygroscopic.
• Commercial tomographs using BGO reach a spatial resolution of
approximately 4mm.
• Presently tomographs with a new scintillator LSO (lutetium
oxyorthosilicate) are built.

61
5 PET
• A scatter coincidence is a detected event where
one or both photons are deflected by Compton
scattering and are therefore assigned to a
wrong coincidence line.
• Scattered coincidences may reach the same
amount as true events and very elaborate
correction algorithms have become necessary
to subtract scatter contributions for accurate
quantitative results.
62
5 PET
• A random coincidence is an event that
two photons from different decays are
detected during the short coincidence
time window.
• Random coincidences can be subtracted
online using a second delayed coincidence
window.
63
5 PET
• After correction for scatter and random events,
attenuation and dead time, an image of the activity
distribution can be reconstructed.
• Originally this was done with standard 2D filtered
backprojection algorithms giving a stack of transverse image
slices.
• With 3D data acquisition, this was extended to volume
reconstruction, which required hours of computing time.
Therefore the algorithms with the rapid developments in
computer hardware, iterative 3D reconstruction are becoming
routinely feasible. 64
™ ADAC’s GSO PET
ALLEGRO

65
PET/CT

66
PET/MRI

67
Micro-PET

68
micro-PET micro-PET/CT

69
Comparison of PET and SPECT

• The advantages of PET are superior sensitivity and


resolution and a far greater flexibility of
incorporating positron labels into biomolecules.

• PET scanners are considerably more expensive


than SPECT systems and also require the presence
of an onsite cyclotron for a full range of application.
70
Comparison of PET and SPECT
• SPECT has significant cost advantages. SPECT
systems are smaller and easier to place within
hospitals.
• SPECT has a singular advantage in being
applicable to the most commonly performed
procedures in nuclear medicine, including
myocardial perfusion imaging with either
201Th( thallium) or 99mTc.
71
Comparison of PET and SPECT

• Hybrid PET-CT scanners hits allowed for the


direct correlation of the functional information
available from PET and the anatomical
information from CT.
• These devices place the CT scan directly in front of
the PET scanner.

72
Comparison of PET and SPECT
• The helical CT scan is acquired first, followed
by the PET scan.
• The CT scan can then provide both a
transmission scan for attenuation correction as
well as anatomical correlation. Because the CT
scan can be acquired must faster than a
traditional PET transmission scan, the use of
PET-CT can substantially increase patient
throughput.
73
74
Content of nuclear medicine
instrumentation
• 1 Principle to Detect and Measure • 2.3 photosensitive material
the Radiation detector
– Ionization • 2.4 Semi-conductor detector:
– Scintillation
– Chemical Mechanism
(sensitization) • 3 Type
– Gamma Counter
• 2 Detector and electronic circuit – Liquid Scintillation Counter
– 2.1 Ionizing detector: Ion – Personnel Monitoring
Chamber, Geiger-Mueller Tube: • SPECT, SPECT-CT
– 2.2 Scintillation Detector • PET,PET-CT/MRI
• 1 Scintillator
• 2 lightguide
• [Link] Tube 75
• 3 Preamplifier
•Thank you!

76
RADIOPHARMACEUTICALS
(RADIOACTIVE DRUGS)

1
ORIENTATION
• Radiopharmacy is a discipline concerned with the
preparation and quality control of
radiopharmaceuticals.
• A radiopharmaceutical is a radioactive compound
used for the diagnosis and therapeutic treatment of
human diseases.
• Radiopharmaceuticals are used in the hospital
department of nuclear medicine or in research institutes.
• Most radiopharmaceuticals are used for diagnostic
purposes, some for therapeutic or palliative use.

2
ORIENTATION
• For diagnosis essentially two techniques are used: SPECT (single-
photon emission computed tomography) and PET (positron emission
tomography). The radiopharmaceutical accumulates in target tissues
and emits gamma radiation that can be detected by imaging
instruments.
• Therapeutic or palliative use requires higher dosages of alpha- or
beta- emitting radiopharmaceuticals.

3
ORIENTATION

4
ORIENTATION
Components of radiopharmaceuticals
• radionuclides
• non radioactive labeled substances
Main features of radiopharmaceuticals
• 1. Radioactive
• 2. Unconstant
• 3. Self radiation decomposition
• 4. Few amount

5
RADIONUCLIDES

• Radionuclides are the most important components of radiopharmaceuticals.


• Desirable properties of radionuclides in radiopharmaceuticals: Relatively
short decay times (half-lives from hours to days) and ease of incorporation
in the final molecule.
1. The energy of the emitted radiation ranges from about 150 (kev) (γ-photons
for diagnostics) to around 1,000 kev (β-particles for therapy).
2. The newer imaging technique of PET uses radionuclides with half-lives going
down to 2 min, emitting positrons that annihilate to γ-photons of 511 kev.

6
RADIONUCLIDES
• Production of radionuclides

Nuclear reactors

Radionuclide Accelerator (Cyclotron)


sources

Radionuclide generator
7
RADIONUCLIDES
• Production of radionuclides
1. Nuclear reactor
There are various radionuclides from reactor production
which cost less. It is the main source of the current medical
radionuclides. Most of the radionuclides produced by the
reactor are abundant neutrons.

8
RADIONUCLIDES
• Production of radionuclides
1. Nuclear reactor

9
RADIONUCLIDES
• Production of radionuclides
1. Nuclear reactor
Radionuclides Half life(T1/2) Nuclear reaction

3H 12.3y 6Li(n, α)3H


14C 5730y 14N(n, p)14C
32P 14.3d 31P(n, γ)32P

89Sr 50.5d 88Sr(n, γ)89Sr


(strontium)
99Mo 2.75d 98Mo(n, γ)99Mo; 235U(n, f)99Mo
(Molybdenum)
125I 60.1d 124Xe(n, γ)125Xe→125I

131I 8.04d 130Te(n, γ)131Te→131I

133Xe 5.24d 235U(n, f)133Xe


(Xenon)
186Re 90.6h 185Re(n, γ)186Re 10
(Rhenium)
153Sm 46.7h 152Sm(n, γ)153Sm
( Samarium)
RADIONUCLIDES
• Production of radionuclides
1. Nuclear reactor
2. Cyclotron
Cyclotron can accelerate charged particles (such as proton, deuteron and
alpha particles) to cause nuclear reaction by current and magnetic field. This
process can produce radionuclides, and these radionuclides are generally poor
neutron with short life.
This type of radionuclide is suitable for SPECT and PET imaging. For the PET,
the radionuclides have the characteristics of the emission of the positron and short
life, such as 11C (20.3min), 13N (10min)nitrogen, 15O (2.1min), 18F (109.8min), etc.

11
RADIONUCLIDES
• Production of radionuclides
1. Nuclear reactor
2. Cyclotron

12
RADIONUCLIDES
• Production of radionuclides
1. Nuclear reactor
2. Cyclotron
Radionuclides Half life(T1/2) Nuclear reaction
11C (Carbon-11) 20.3min 14N(p,α)11C

13N (Nitrogen-13) 10min 16O(p, α)13N


15O (Oxygen-15) 2.1min 14N(d, n)15O ; 15N(p, n)15O
18F (Fluorine-18) 110min 18O(p, n)18F; 20N(d, α)18F
67Ga (Gallium-67) 3.26d 65Cu(α,2n) 67Ga

111In (Indium-111) 2.80d 109Ag(α,2n)111In; 111Cd(p, 111In


n)
123I (Iodide-123) 13.2d 124Te(p, 2n)123I
13
201Tl (Thallous-201) 73.2h 203Tl(p, n)201Pb→201Tl
RADIONUCLIDES
• Production of radionuclides
1. Nuclear reactor
2. Cyclotron
Main Features:
• + or γ ray emission
• Short half-life
• High specific activity
• Wide use
The positron emission of stable isotopes are the main components of the body, such
as 11C, 13N, 15O and so on. They have short half-life and can emit beta+ particle
and annihilates to two gamma rays of 511 kev. So they have been widely used in
life science.
14
RADIONUCLIDES
• Production of radionuclides
1. Nuclear reactor
2. Cyclotron
3. Radionuclide generator
The generator is a device for the production of radionuclides, which
can produce regularly the daughter radionuclides by decay from the
radioactive parent nucleus. The parent radionuclide half-life is long, the
half-life of the daughter radionuclide is generally short, and the nuclear
generator is often called the "cow".

15
RADIONUCLIDES
• Production of radionuclides
1. Nuclear reactor
2. Cyclotron
3. Radionuclide generator

Molybdenum-99/Technetium-99m “Cow”

 
99
42 Mo 99 m
43Tc  Tc   (140keV )
99
43
66 h 6h 16
RADIONUCLIDES
• Production of radionuclides
1. Nuclear reactor
2. Cyclotron
3. Radionuclide generator

Molybdenum-99/Technetium-99m Cow
Germanium-68/Gallium-68 generator
Tungsten-188/rhenium-188 generator

17
RADIONUCLIDES
• Production of radionuclides
• Common radionuclides and their use
Diagnostic use Diagnostic use Therapeutic/
(SPECT) (PET) palliative use
51Cr(Chromium) 11C 32P

67Ga(Gallium) 13N 89Sr(strontium)

81mKr(Krypton) 15O 90Y(Yttrium)

99mTc 18F(Fluorine) 131I

111In(Indium) 68Ga(Gallium) 153Sm( Samarium)


123I 82Rb(rubidium) 177Lu( Lutetium)
133Xe(Xenon) 89Zr(Zirconium) 188Re(Rhenium)
18

201Tl(Thallous) 124I 223Ra(Radium)


RADIOPHARMACEUTICALS
Definition of a radiopharmaceutical
• A radiopharmaceutical is a radioactive compound used for the diagnosis and
therapeutic treatment of human diseases. A radiopharmaceutical has two
components: a radionuclide and a pharmaceutical.
• In nuclear medicine nearly 95% of the radiopharmaceuticals are used for
diagnostic purposes, while the rest are used for therapeutic treatment.
• Because they are administered to humans, they should be sterile and pyrogen
free, and should undergo all quality control measures required of a
conventional drug.
• Other terms: radiotracer, radiodiagnostic agent, tracer

19
RADIOPHARMACEUTICALS
Ideal radiopharmaceutical
• Easy availability
• Short effective half-life equation

• Particle emission
• Suitable energy
• High target-to-nontarget activity ratio

20
RADIOPHARMACEUTICALS
Radiopharmaceutical mechanisms of localization
Mechanism Applications or examples
Compartmental localization Blood pool imaging,
direct cystography
Passive diffusion Blood–brain barrier breakdown, glomerular
(concentration dependent) filtration, cisternography

Capillary blockade (physical Perfusion imaging of lungs


entrapment)
Physical leakage from a Gastrointestinal bleeding, detection of urinary tract
lumina compartment or biliary system leakage
Metabolism Glucose, fatty acids
Active transport (active Hepatobiliary imaging, renal tubular function,
cellular uptake) thyroid and adrenal imaging 21
RADIOPHARMACEUTICALS
Radiopharmaceutical mechanisms of localization
Mechanism Applications or examples
Chemical bonding and Skeletal imaging
adsorption
Cell sequestration Splenic imaging (heat-damaged red blood cells),
white blood cells
Receptor binding and Adrenal medullary imaging, somatostatin receptor
storage imaging
Phagocytosis Reticuloendothelial system imaging
Antigen-antibody Tumor imaging

22
RADIOPHARMACEUTICALS
Radiopharmaceutical mechanisms of localization

Mechanism Applications or examples


Multiple mechanisms
Perfusion and active Myocardial imaging
transport
Active transport and Thyroid uptake and imaging
metabolism
Active transport and Hepatobiliary imaging, salivary gland imaging
secretion

23
RADIOPHARMACEUTICALS
Methods of radiolabeling

24
RADIOPHARMACEUTICALS
Important factors in labeling
• Efficiency of the labeling process
• Chemical stability of the product
• Denaturation or alteration变性
• Isotope effect
• Carrier-free or no-carrier-added state
• Storage conditions
• Specific activity比活度
• Radiolysis 辐射分解
• Purification and analysis
• Shelf life保存限期 25
QUALITY CONTROL
OF RADIOPHARMACEUTICALS
• Since radiopharmaceuticals are intended for administration to humans, it is
imperative that they undergo strict quality control measures.
• Quality control involves several specific tests and measurements that ensure the
purity, potency, product identity, biologic safety, and efficacy of
radiopharmaceuticals.
• All quality control procedures that are applied to nonradioactive
pharmaceuticals are equally applicable to radiopharmaceuticals; in addition,
tests for radionuclidic purity and radiochemical purity have to be carried out.

26
QUALITY CONTROL
OF RADIOPHARMACEUTICALS

• Physicochemical tests
• Biological tests

27
QUALITY CONTROL
OF RADIOPHARMACEUTICALS
Physicochemical tests
• Physical characteristics: color, state(solution, colloid)
• pH and ionic strength: the ideal pH=7.4, proper ionic strength, isotonicity, and osmolality

• Radionuclidic purity: the fraction of the total radioactivity in the form of the
desired radionuclide present in a radiopharmaceutical
• Radiochemical purity: the fraction of the total radioactivity in the desired
chemical form in the radiopharmaceutical.
• Chemical purity: the fraction of the material in the desired chemical form, whether or not all of it is in the
labeled form.
• Radioassay放射分析

28
QUALITY CONTROL
OF RADIOPHARMACEUTICALS
Physicochemical tests
• Radiochemical purity
A number of analytical methods are used to detect and determine the radiochemical
impurities in a given radiopharmaceutical.
• Precipitation
• Paper and instant thin-layer chromatography (ITLC)
• Gel chromatography
• Paper or polyacrylamide gel electrophoresis
• Ion exchange
• Solvent extraction
• High-performance liquid chromatography (HPLC)
• Distillation

29
QUALITY CONTROL
OF RADIOPHARMACEUTICALS
Physicochemical tests
• Radiochemical purity
• Paper and instant thin-layer chromatography (ITLC)
• A small aliquot of the radiopharmaceutical preparation is spotted on a paper (whatman
paper stripor an ITLC strip.
• Then chromatography is carried out by dipping the spotted strip into an appropriate solvent
contained in a jar or a chamber.
• The commonly used solvents for chromatography of 99mTc-complexes are 85% methanol,
acetone, methylethyl ketone (MEK), 0.9% NaCl solution(sodium chloride), and water.
• The strip is dipped in such a way that the spot remains above the solvent.
• Varying solubilities of different components in a solvent cause the individual components to
move at different speeds and to appear at different distances along the paper or ITLC strip.

30
QUALITY CONTROL
OF RADIOPHARMACEUTICALS
Physicochemical tests
• Radiochemical purity
• Paper and instant thin-layer chromatography (ITLC)

Typical chromatogram obtained with ITLC-SG


paper and acetone,
showing two peaks: one at the solvent front for
free 99mTcO4- and the other at the origin for
both hydrolyzed and bound 99mTc-labeled
compounds.

31
QUALITY CONTROL
OF RADIOPHARMACEUTICALS
Physicochemical tests
• Radiochemical purity
• Paper and instant thin-layer chromatography (ITLC)
Rf value: the ratio of the distance traveled by the component to the distance
traveled by the solvent front from the original point of application of the sample.

For example, in the analysis of 99mTc-pyrophosphate(MDP), the ITLC method using 85% methanol or
acetone and ITLC-SG paper gives only two peaks – bound and hydrolyzed 99mTc at the origin (Rf =0) and
free 99mTc at the solvent front (Rf =1.0).

32
QUALITY CONTROL
OF RADIOPHARMACEUTICALS
Physicochemical tests
• Radiochemical purity
• Paper and instant thin-layer chromatography (ITLC)
Rf value: the ratio of the distance traveled by the component to the distance
traveled by the solvent front from the original point of application of the
sample.
For example, in the analysis of 99mTc-pyrophosphate, the ITLC method using 85% methanol or acetone and
ITLC-SG paper gives only two peaks – bound and hydrolyzed 99mTc at the origin (Rf =0) and free 99mTc at
the solvent front (Rf =1.0).

If, however, Whatman No. 1 paper and saline are used in ITLC chromatography, the three components can
be separated: the bound 99mTc at the solvent front, the hydrolyzed 99mTc at the origin, and the free 99mTc at
Rf = 0.7.
33
QUALITY CONTROL
OF RADIOPHARMACEUTICALS
Physicochemical tests
• Radiochemical purity
• Paper and instant thin-layer chromatography (ITLC)
Chromatographic data of 99mtc-labeled radiopharmaceuticals

34
QUALITY CONTROL
OF RADIOPHARMACEUTICALS
Physicochemical tests
• Radioassay
The amount of radioactivity of a radiopharmaceutical before dispensing, as well as
that of each individual dosage before administration to patients, must be determined.
These activity determinations are carried out by means of a radionuclide dose
calibrator.

35
QUALITY CONTROL
OF RADIOPHARMACEUTICALS
Biological tests
• Sterility
• Apyrogenicity
• Toxicity

Biological tests are carried out essentially to examine the sterility,


apyrogenicity, and toxicity of radiopharmaceuticals before human
administration. These tests for radiopharmaceuticals are identical to
those for conventional pharmaceuticals.

36
NUCLEAR PHARMACY

• Concept
• Operation of a nuclear pharmacy

37
NUCLEAR PHARMACY
Concept a place
• In a nuclear pharmacy radiopharmaceuticals are prepared, stored, and dispensed primarily for
human use, just as regular drugs are in a pharmacy.

• The nuclear pharmacy is staffed with trained personnel such as radiopharmacists and radiochemists,
that is, chemists or pharmacists with special training in radiopharmaceutical chemistry.

• The nuclear pharmacy may serve as a center for education and training of pharmacy and nuclear
medicine technology students and engage in basic research in the design and development of new
radiopharmaceuticals.

• Here the remedy for any adverse reaction in humans due to the administration of
radiopharmaceuticals is sought and found.

• The nuclear pharmacists can provide education and consultation to the patients and health care
personnel in this field.

38
NUCLEAR PHARMACY
Operation of a nuclear pharmacy
(1) Receiving and monitoring of radioactive packages
(2) Preparation of radiopharmaceuticals
(3) Quality control of radiopharmaceuticals
(4) Storage
(5) Dispensing
(6) Radioactive waste disposal
(7) Infectious waste disposal 39
NUCLEAR PHARMACY
Operation of a nuclear pharmacy
(4) Storage
• All radiopharmaceuticals should be properly stored so that they are not degraded
by light or temperature. (99mTc-MAA 2-4℃,99mTc-SC room temperature)
• Since radiation exposure is a serious problem in the nuclear pharmacy, the vials or
syringes containing radiopharmaceuticals must be stored in lead containers or behind
lead shields.
• To prevent the production of bremsstrahlung in high Z materials such as lead, 32P
(phosphorus)-labeled compounds and 89Sr-SrCl2 (Strontium chloride)are
stored in low Z material containers such as plastic or lucite containers.

40
NUCLEAR PHARMACY
Operation of a nuclear pharmacy
(5) Dispensing Pediatric dosages

the Society of Nuclear


Medicine

41
DIAGNOSTIC USES OF
RADIOPHARMACEUTICALS IN NUCLEAR
MEDICINE
Central nervous system
Brain imaging
• The principle of brain imaging is governed by a mechanism called the blood–brain barrier
(BBB), which excludes many substances from entering the brain from the blood.
• Based on the principle of BBB, radiopharmaceuticals for brain imaging can be broadly grouped
into two categories: diffusible and nondiffusible.
• Diffusible tracers are typically lipophilic and readily cross the BBB.
• Nondiffusible tracers are hydrophilic and polar and cannot cross the BBB except in abnormal
tissues where the BBB is broken.

42
DIAGNOSTIC USES OF
RADIOPHARMACEUTICALS IN NUCLEAR
MEDICINE
Central nervous system
Brain imaging
Examples:
• Diffusible tracers:
99mTc-HMPAO (99mTc-hexamethylpropylene amine oxime)
99mTc-ECD (99mTc-ethylcysteinate dimer)
18F-FDG (18F-fluorodeoxyglucose)

• Nondiffusible tracers:
99mTcO - , 201Tl , 99mTc-DTPA
4
43
DIAGNOSTIC USES OF
RADIOPHARMACEUTICALS IN NUCLEAR
MEDICINE
Central nervous system
Radiopharmaceuticals for brain imaging

44
DIAGNOSTIC USES OF
RADIOPHARMACEUTICALS IN NUCLEAR
MEDICINE
Central nervous system
Baseline and ictal images of an
epilepsy patient obtained by
99mTc-ECD

SPECT imaging in transverse,


coronal and sagittal projections.
Seizure focus is indicated
by white arrows at right lateral
and dorsal lateral anterior
parietal regions.
Red arrows indicate the prior
surgical scar.

45
DIAGNOSTIC USES OF
RADIOPHARMACEUTICALS IN NUCLEAR
MEDICINE
Central nervous system

18F-FDG PET images of an epilepsy patient in transverse and coronal


projections showing bilateral temporal lobe hypometabolism.
46
DIAGNOSTIC USES OF
RADIOPHARMACEUTICALS IN NUCLEAR
MEDICINE
Central nervous system
Brain imaging
Cisternography
• Cisternography is employed in the investigation of the rate of
formation, flow, and resorption of CSF(Cerebrospinal Fluid ).
(hydrocephalus, CSF leakage)
• Radiopharmaceutical: 111In-DTPA(Indium), 99mTc-DTPA

47
DIAGNOSTIC USES OF
RADIOPHARMACEUTICALS IN NUCLEAR
MEDICINE
Thyroid
Radiopharmaceuticals and imaging techniques
• 131I- or 123I-Sodium Iodide (oral administration)
1. The iodide uptake test:

10–15 μCi (0.37–0.56 MBq) 131I-NaI , or 100 μCi (3.7MBq) 123 I-NaI . Test is performed 2h, 6h, 24h after oral
administration.

2. Thyroid scan:
100 μCi (3.7 MBq) 131 I-NaI , or 300 μCi (11.1 MBq) 123 I-NaI. Images are taken 24h after oral administration
-
99mTc-Sodium Pertechnetate (99mTcO4 , intravenous administration)
10 mCi (370 MBq) 99mTcO -, Images are taken 10-30min after injection.
4

48
DIAGNOSTIC USES OF
RADIOPHARMACEUTICALS IN NUCLEAR
MEDICINE
Thyroid

Thyroid images obtained with 131I (24 h after oral administration) and 99mTc (30min
after injection) and showing a “hot” nodule in the upper right lobe. Both images are
similar in the distribution of radioactivity except that there is slightly more uptake of
131I in the left lobe. 49
DIAGNOSTIC USES OF
RADIOPHARMACEUTICALS IN NUCLEAR
MEDICINE
Lung
Radiopharmaceuticals for lung imaging

50
DIAGNOSTIC USES OF
RADIOPHARMACEUTICALS IN NUCLEAR
MEDICINE
Lung

Normal lung images obtained with 99mTc-MAA in different Lung images obtained with 99mTc-MAA in different
projections. The distribution of radioactivity is uniform in projections indicating multiple pulmonary emboli in both
both lungs. lobes of the lungs.
51

RL right lateral; LPO left posterior oblique; RPO right posterior oblique; LL left lateral; ANT anterior; POST posterior.
DIAGNOSTIC USES OF
RADIOPHARMACEUTICALS IN NUCLEAR
MEDICINE
Lung

Lung ventilation images obtained with 99mTc-DTPA aerosol


Normal lung ventilation images obtained with indicating multiple defects in a patient with chronic
99mTc-DTPA aerosol obstructive pulmonary disease(COPD).Due to varying
degrees of bronchial injury and incomplete obstruction,
radioactive particles deposit in the airway, forming
52
irregular radioactive hot spots.
DIAGNOSTIC USES OF
RADIOPHARMACEUTICALS IN NUCLEAR
MEDICINE
Liver
Radiopharmaceuticals for liver imaging

53
DIAGNOSTIC USES OF
RADIOPHARMACEUTICALS IN NUCLEAR
MEDICINE
Liver
Normal hepatobiliary images obtained
with 99mTc-DISIDA in different projections.
The gallbladder is seen within 15 min
after administration of the radioactivity.
The radioactivity clears almost
completely from the hepatobiliary system
into
the gut within 45 min.

54
DIAGNOSTIC USES OF
RADIOPHARMACEUTICALS IN NUCLEAR
MEDICINE
Spleen
• 99mTc-sulfur colloid
• 99mTc-albumin colloid
2–3 mCi (74–111 MBq), injected intravenously,
imaging is begun about 15–30 min after injection

• 99mTc-Labeled Red Blood Cells


A dosage of 2–3 mCi (74–111 MBq) heat-denatured 99mTc-labeled red blood cells is
injected and imaging can be performed 30–60 min after injection to demonstrate the
structure of the spleen and any abnormality therein.

55
DIAGNOSTIC USES OF
RADIOPHARMACEUTICALS IN NUCLEAR
MEDICINE
Kidney
Radiopharmaceuticals for renal imaging

56
DIAGNOSTIC USES OF
RADIOPHARMACEUTICALS IN NUCLEAR
MEDICINE
Kidney

Effective Renal Plasma Flow (ERPF)


99mTc-MAG3 is commonly used for the measurement of ERPF.
It is primarily secreted by the tubules to the extent of greater than 90%.

Glomerular Filtration Rate (GFR)


99mTc-DTPA is used for the measurement of GFR.
It is entirely filtered by glomeruli in the kidneys.

57
DIAGNOSTIC USES OF
RADIOPHARMACEUTICALS IN NUCLEAR
MEDICINE
Skeleton
• 99mTc-Phosphonate Compounds
99mTc-MDP、 99mTc-HDP

10–20 mCi (370–740 MBq) ,is injected intravenously ,


scanning is performed 2–3 h after injection.

• 18F-Sodium Fluoride ( 18F-NaF )


For PET imaging

4 mCi (148MBq) ,is administered intravenously,


imaging is performed 15–30 min after injection.
58
DIAGNOSTIC USES OF
RADIOPHARMACEUTICALS IN NUCLEAR
MEDICINE
Heart
Radiopharmaceuticals for myocardial imaging

59
DIAGNOSTIC USES OF
RADIOPHARMACEUTICALS IN NUCLEAR
MEDICINE
Heart
Perfusion Imaging
Comparative characteristics of different perfusion radiopharmaceuticals

60
DIAGNOSTIC USES OF
RADIOPHARMACEUTICALS IN NUCLEAR
MEDICINE
Heart
Perfusion Imaging
• 99mTc-Sestamibi (99mTc-MIBI)甲氧基异丁基异睛
is a lipophilic cationic (1+) 亲脂性阳离子的complex that accumulates in the
99mTc-sestamibi

myocardium by passive diffusion被动扩散, not transported by the Na+–K+–ATPase pump.

• 201Tl-Thallous Chloride氯化亚铊
Thallous ion behaves like K+(potassium ion), which is transported through the cell membrane
by active transport by the Na+–K+–ATPase enzyme.

61
DIAGNOSTIC USES OF
RADIOPHARMACEUTICALS IN NUCLEAR
MEDICINE
Heart Transverse 18F-FDG PET image of
the heart after glucose loading
Metabolic Imaging demonstrating increased FDG
uptake in the posterolateral fixed
18F-Fluorodeoxyglucose (18F-FDG) defect identified by 82Rb
rubidium (equilibrium) PET image
123I-labeled fatty acids to indicate the viability of the
tissues.
13N-labeled Glucose was administered 1 h
amino acid before the administration of 18F-
FDG, and PET imaging was
performed 40 min after the
administration of 18F-FDG.

62
DIAGNOSTIC USES OF
RADIOPHARMACEUTICALS IN NUCLEAR
MEDICINE
Heart
Myocardial Infarct Imaging
99mTc-Pyrophosphate

10–15 mCi (370–555 MBq) ,injected intravenously.


Imaging is performed 1–2 h after administration.
Myocardial infarct image obtained
with 99mTc-pyrophosphate in
different projections 2 h after
injection, indicating increased
uptake in the infarcted area at the
anterior apical left ventricular wall.
Imaging performed 24 h after
onset of infarction.

63
DIAGNOSTIC USES OF
RADIOPHARMACEUTICALS IN NUCLEAR
MEDICINE
Heart
Cardiac Innervation Imaging
123I-MIBG

MIBG behaves like norepinephrine (NE) as far as the uptake and storage
mechanism is concerned.

Radionuclide Angiography
• First-Pass Method
99m
Tc-pertechnetate, 99mTc-DTPA, or any 99mTc-labeled compound

• Gated Equilibrium Cardiac Blood Pool Method


99mTc-RBC

• Radionuclide Stress Ventriculography 99mTc-DTPA


64
DIAGNOSTIC USES OF
RADIOPHARMACEUTICALS IN NUCLEAR
MEDICINE
Tumor imaging
Radiopharmaceuticals for tumor imaging

65
DIAGNOSTIC USES OF
RADIOPHARMACEUTICALS IN NUCLEAR
MEDICINE
Tumor imaging
18F-FDG(fluorine) Whole Body Imaging

Whole body 18F-FDG


and CT images of a
patient with esophageal
cancer. Fusion of
attenuation-corrected PET
and CT images in
different projections
(transverse, coronal and
sagittal) delineates描绘
the tumor remarkably.

66
DIAGNOSTIC USES OF
RADIOPHARMACEUTICALS IN NUCLEAR
MEDICINE
Lymphoscintigraphy
99mTc-SC(Sulfur colloid)、99mTc-albumin colloid (nanocolloid)

450μCi (16.7 MBq), Injected subcutaneously,


Imaging time depends on the tumor type.

Gastric Emptying Imaging


In one solid meal, approximately 1 mCi(37 MBq) 99mTc-SC is mixed with a bowl of oatmeal.

In a liquid meal, 1 mCi (37 MBq) 99mTc-DTPA or 0.5 mCi (18.5 MBq)111In-DTPA in 300 ml water
solution is commonly used for drinking.

67
DIAGNOSTIC USES OF
RADIOPHARMACEUTICALS IN NUCLEAR
MEDICINE
Meckel’s Diverticulum Imaging
99mTc-pertechnetate ( 99mTcO -)
4

Gastrointestinal Bleeding Detection


99mTc-SC 、99mTc-RBCs

Inflammatory Diseases and Infection Imaging

67Ga-Citrate

111In- or 99mTc-Leukocytes
68
DIAGNOSTIC USES OF
RADIOPHARMACEUTICALS IN NUCLEAR
MEDICINE
Parathyroid Imaging (hyperparathyroidism)

Several imaging protocols are in use for the diagnosis of abnormal


parathyroid.

Combinations such as 99mTcO4- /201Tl, 123I/201Tl and 123I/99mTc-sestamibi


are used as the dual isotopes.

In another technique, a single dosage of 10–20 mCi (370–740


MBq) 99mTc-sestamibi is injected and the patient’s parathyroid is
first imaged 10–15 min postinjection and then 2–3 h later.

69
THERAPEUTIC USES
OF RADIOPHARMACEUTICALS
IN NUCLEAR MEDICINE
Treatment of Hyperthyroidism and Thyroid Cancer
131I-NaI

Treatment of Bone Pain (bone metastasis)


89Sr-Strontium Chloride

153Sm(samarium)-EDTMP

32P(phosphorus)-Sodium Orthophosphate

70
THERAPEUTIC USES
OF RADIOPHARMACEUTICALS
IN NUCLEAR MEDICINE
Treatment of Liver Cancer
90Y(yttrium)-TheraSpheres、 90Y-SIR-Spheres

Treatment of Non-Hodgkin’s Lymphoma


90Y-Ibritumomab Tiuxetan
131I-Tositumomab

Polycythemia Vera and Leukemia

32P(phosphorus)-sodium orthophosphate

71
PROGRESS IN THE RESEARCH OF
RADIOPHARMACEUTICALS

• 1. Receptor Imaging Agent


• 2. Hypoxia Imaging Agent
• 3. Cell Apoptosis Imaging Agent
• 4. Amyloid Plaque Imaging Agent
• 5. Dopamine Transporter Imaging Agent

72
Receptor Imaging Agent

• It has such advantages as: high affinity, high specificity,


reaching the target organ speed, fast blood clearance, no
immune response.

• At present, it has been widely used in the diagnosis of tumor,


heart and nervous system diseases.

73
Receptor Imaging Agent
• Dopamine receptor imaging agents are often used in the diagnosis of
parkinson's disease and schizophrenia.

• 11C and 18F labeled octreotide are applied for tumor growth of somatostatin
receptor imaging and therapy, and has been used in the diagnosis and
treatment of thyroid cancer, gastrointestinal and pancreatic neuroendocrine
tumor, pheochromocytoma, and small cell lung cancer.

• Estrogen receptor imaging has been used in the diagnosis of primary and
metastatic lesions of breast cancer and efficacy monitoring (18F-FES).

74
Hypoxia Imaging Agent

• In solid tumors, the growth of most tumors is very rapid, the growth rate of
blood vessels can not meet the need of the growth of tumor, so that the
blood supply is seriously insufficient, there is lack of oxygen phenomenon.

• Oxygen deficient cells are not sensitive to radiotherapy and


chemotherapy, making it difficult to cure and relapse.

75
Hypoxia Imaging Agent

• Marked by 99mTc is mainly nitroimidazole硝基咪唑 hypoxia imaging


agent.

• For the majority of 18F labeled 2-nitroimidazole derivatives衍生物.

• Oxygen levels in tumor patients were detected by hypoxia imaging


before and after treatment, the therapeutic effect can be evaluated,
and it is helpful to make the treatment plan.

76
Cell Apoptosis Imaging Agent

• Cell apoptosis is an important mechanism to determine


the development and balance of the organism.

• If this mechanism has dysfunction or loss of control, the


pathological changes of tumor and neurodegenerative
diseases will be caused.

77
Cell Apoptosis Imaging Agent

• Apoptosis imaging study of major diseases have a deeper


understanding, it will also to clinical treatment plan formulation,
curative effect judgment has important significance, such as cancer,
heart disease and organ transplantation disease molecular biology
behavior.

• 99mTc-HYNIC-Annexin V is the most promising cell apoptosis imaging


agent, which has been used in clinical research.

78
Amyloid Plaque Imaging Agent

• Alzheimer's disease (AD) is one of the most common forms of senile


dementia.
• The pathogenesis of AD is still not quite sure.
• Methods and means of early diagnosis and treatment of AD disease
has become the hotspot in the field of medicine.
• Amyloid plaque imaging agent may help realize the early diagnosis
of AD, evaluate the development of the disease and the treatment
effect, and carry on the pathology research of AD.

79
Dopamine Transporter Imaging Agent

• Dopamine transporter imaging agents are mainly used for diagnosis and
treatment of parkinson's disease and drug addiction (drug abuse);

• In the series of benzene with 99mTc supporting derivatives imaging agent and
99mTc-TRODAT 1 effect is the best, it has become the world's first successful for
central nervous system of human brain dopamine transporter SPECT 99mTc
labeled receptor drugs.

80
DEFINITIONS
Alpha radiation Ionising radiation by alpha particles
(4He2+-ions). In comparison with beta and gamma
radiation, alpha radiation
has the least penetrating power and the highest
linear energy transfer.
Alpha emitter Radionuclide that decays to a more stable nuclide
by emission of an alpha particle.
Annihilation radiation Two gamma rays with an energy of 511 keV that
are emitted at an angle of 180°after collision of
a positron
with an electron.
Becquerel Unit of radioactivity: 1 Becquerel(Bq) is equivalent
with 1 disintegration per second (kBq =1,000 Bq,
MBq=106 Bq).
81
DEFINITIONS
Beta radiation Ionising radiation by beta+ (=positron)
or beta- (=electron) particles.
Beta emitter Radionuclide that decays to a more stable
nuclide by emission of a beta+ (=positron) or
a beta- (=electron) particle.
Cyclotron Equipment in which charged particles, after
acceleration in a circular pathway, are
directed onto a target for evoking a nuclear
reaction.

82
DEFINITIONS
Decay Spontaneous reaction of a radionuclide to form another
(radio)nuclide accompanied by the release of ionising
radiation.
Electronvolt (eV) Kinetic energy gained by an electron when accelerated
through a potential field of 1 volt (keV=1,000 eV).
Gamma radiation High energy photons that are emitted during radioactive
decay.
Gamma emitter Radionuclide that emits gamma rays during radioactive
decay.
Generator A device in which a daughter radionuclide with a shorter
half-life is separated from a mother radionuclide with a
longer half-life.

83
DEFINITIONS
Half-life The characteristic of a radionuclide that defines the
time during which the radioactivity of a radionuclide
is reduced to half of its original value.
Kit for labelling Composed set of all non-radioactive reagents in
appropriate quantities for the preparation of a
specific radiopharmaceutical.
Magnetic resonance A medical imaging technique to investigate the
imaging (MRI) anatomy and physiology of the body using strong
magnetic fields.
Nuclear reactor Installation for the production of radionuclides by
nuclear fission of e.g. 235uranium.

84
DEFINITIONS
PET Positron emission tomography: an imaging technique that
makes use of a radiopharmaceutical that is labelled with a
positron emitter (e.g. 11C, 13N, 18F).
Positron A beta+ particle that, after collision with an electron,
annihilates to two gamma rays of 511 keV.
Radioactivity Spontaneous process in which an unstable radionuclide
transforms to a more stable (radio)nuclide releasing energy
in the form of particles (alpha or beta particles) or photons
(gamma rays).
Radiochemical Any compound containing one of more atoms of a
radioactive isotope.

85
DEFINITIONS

Radiochemical purity Fraction of the total radioactivity present in the


desired radiochemical form.
Radiolabelling Process of attaching a radionuclide to a non-
radioactive molecule.
Radionuclide An unstable nuclide that decays spontaneously by the
emission of particles (alpha or beta particles) or
photons (gamma rays).
Radionuclidic purity Fraction of the total radioactivity present as the
desired radionuclide.

86
DEFINITIONS

Radiopharmaceutical A pharmaceutical substance that contains one


or more radionuclides.
SPECT Single-photon emission computed tomography:
an imaging technique that makes use of a
radiopharmaceutical that is labelled with a
gamma emitter.

87
88
Genitourinary System

1
Introduction
 Radioisotope imaging of the genitourinary tract
has become an invaluable asset to clinicians in
the evaluation of renal parenchymal and
urologic abnormalities.
 The unique combination of functional and
anatomic assessment provided by nuclear
imaging makes it the diagnosis test of choice in
many situations.

2
PHYSIOLOGY
 Urinary system consists of kidneys, ureter, bladder and
urethra.

 The kidney is the organ of the urinary tract.

 The rest is the storage of urine and micturition organs .

 The main physiological functions of urinary system are:

End product of excretion of human body.

Maintain water, electrolyte and acid-base balance.

3
Genitourinary system

4
 anatomy of kidney

Renal papilae
Renal pyramid

Major renal calices Renal Column

Minor renal calices

Renal pelvis

Fibrous capsule
of kidney

Anatomy of kidney
5
RADIOPHARMACEUTICALS
Radiopharmaceuticals commonly used for evaluating renal
function and anatomy fall into three main categories:
Those excreted by tubular secretion
Those excreted by glomerular filtration
Those bound in the renal tubules for a sufficiently long time
to permit cortical anatomic imaging.
A thorough knowledge of the biodynamics of these classes of
radiopharmaceuticals is essential for choosing the most
appropriate radiopharmaceutical for a particular clinical setting.
6
Glomerular Filtration Agents
 Technetium-99m (99mTc) diethylenetriamine pentaacetic acid
(DTPA) is the only imaging radiopharmaceutical used for the
evaluation of glomerular filtration function. As the DTPA
complex is cleared by the renal glomeruli, serial images may
be obtained that demonstrate sequential visualization of the
kidneys and collecting systems, ureters, and bladder.
Measurement of its excretion can also provide an accurate
estimate of the glomerular filtration rate (GFR).

7
Glomerular Filtration Agents
 The normal GFR is 125 mL/min.
 99mTc-DTPA, the normally administered activity for adults is
about 10 mCi or less.

8
Tubular Secretion Agents
 Technetium-99m–labeled agent mercaptoacetyltriglycine
(mertiatide or MAG3) is protein bound and is cleared
predominantly by the proximal tubules (95%) with minimal
filtration (less than 5%). With an extraction fraction of 40% to
50% (more than twice that of 99mTc-DTPA), it provides more
satisfactory images than does 99mTc-DTPA, especially in patients
with obstruction or impaired renal function.
 For 99mTc-MAG3, the typical administered activity for adults is
about 10 mCi or less. In pediatric patients, doses should be
individually calculated for each patient. 9
Renal Cortical Agents
 The two radiopharmaceuticals used for visualization of the
renal parenchyma are 99mTc-dimercaptosuccinic acid
(DMSA) and, to a lesser extent, 99mTc-glucoheptonate.

Both of these agents bind sufficiently to the renal tubules


to permit renal cortical imaging.

10
Advantages of renal
scintigraphy
1 minimal radiation exposure
2 non-invasive
3 easily reproduced
4 no urine collection necessary
5 can be performed on an out-patient basis
6 few adverse effects reported.

11
Renogram
Principle
 The metabolites代谢物 and useless materials first
filtrated by glomeruli肾小球 or secreted by renal
tubules and then passed outside the body.131I-OIH
is a urinary excretory substance and can be
secreted by renal tubules after injection into the
[Link] renogram is a time-activity curve
obtained during the transit运输,secretion 分泌
excretory排泄 route of 131I-OIH through the kidney
12
Preparation and examination
 In general, patients must drink 500ml water in15min
before test for maintenance of a steady state稳态 of
urine flow.
 When 131I-OIH 5-10μCi is injected into vein as a
bolus,the radioactivity over the both kidneys is
recorded by scintillation probe or detector as long as
20 min,then the time-activity curve (renogram)is
obtained. 13
14
The normal curve involves 3 phases.
Phase a Phase b Phase c
Rapidly rising Funtional phase Excretory phase
vascular
phase
Lasts 30 sec. Rises slowly and Slowly
lasts 5min. descends and
less than 8 min.
The slope and height
Reflects renal of phase b reflects Reflects urinary
perfusion. the velocity and obstruction.
amount of 131I-OIH
accumulating in the
kidney.
Reflects renal
function.
The efficiency of uptake is reflected by the
slope of the ascending portion of the time-activity
curve and by the time at which the peak counts or
T max are reached. Normal curve
15
The rate of disappearance of the tracer from the kidney
is an important indication of tubular function and is
expressed by T1/2. The normal value is showed in Table
1.
Table [Link] values of renogram
Left(min) Right(min)
Tmax 3.24±0.72 3.45±1.13

T1/2 4.94±1.8 5.06±2.27

16
Analysis
 3 phases of normal renogram
 phase a(arrival of tracer)
 phase b(concentration)
 phase c(elimination)
 Quantitive analysis
 peak time(tb)<4.5min
 half time(C1/2)<8min
 15min residue rate<50%
 difference between peak time<1min
 difference between peak value<30%

17
Seven types of abnormal curve
 1.1 Parabola type
The curve rises slowly,gradually falls and Tmax
[Link] suggests the patients suffer from mild renal
insufficiency.
1.2 Low level prolonged type
Height of phase a is lowered ,while phase b and c
merged each [Link] indicates severe renal injury.

18
 1.3 Low level descending type
The curve shows significant low phase a with gradual down
slope ,without phase b and c. Such patients usually have
nonfuntional kidney,representing blood background activity
only .
 1.4 Acute rising type
Phase a is normal, phase b is continued uprising,but phase
c is [Link] this condition, it means urinary obstruction.

19
 1.5 High level prolonged type
Phase a is normal too,and phase b rises [Link]
curve always occurs in urinary obstruction with renal
insufficiency.
1.6 Stepwise drop type
Phase a and b are normal,but phase c drops step by
[Link] is seen in spasmodic ureter.
1.7 Small kidney type
The curve is very similar to the normal one,but the
height of curve is much lower than normal [Link]
presents congenital small kidney or renal failure pattern.

20
21
Evaluation
The renogram is very useful.
1)It can screen for the diagnosis of
renovascual hypertension
2)Investigate obstructive uropathy such as
acute and renal stone
3)Diagnose acute anuria
4) Monitor the therapeutic effect of renal
disease
5)Monitor renal function in renal transplant.
22
Glomerular Filtration
 Definition
 Glomerular filtration rate(GFR):
The plasma volume(ml) filtrated through the
glomerulus per minute .
Normal value: 80-100 ml/min
Increase: In early stage of diabetes.
Decrease: Renal insufficiency, in the late stage
of diabetes,the 3rd stage of hypertension,
azotemia,uremia
23
Effective Renal Plasma Flow(ERPF)
 Definition:
ERPF:
Clearance of the plasma volum(ml) per
minute during the first pass of the injected
material through the kidney .

24
ERPF is a parameter of the renal tubular
function.
Normal value:450 ml/min
Abnormal:
 In acute and chronic nephritis ,ERPF will
decrease.
 Paralleling with the changes of renogram.

 ERPF can monitor therapeutic effect and


rejection of transplant kidney.

25
Normal Position of kidneys
The kidneys are approximately 12 cm
in length and situated
retroperitoneally at the level of T11-
12(thoracic vertebra ),the right
being 1-2cm lower than the [Link]
has one or more main renal arteries
entering at the hilum,dividing into
interlobular arteries,which run
radially out to the cortico-medullary
junction and then into the arcuate
arteries and ultimately through the
afferent arterioles to the glomerular
[Link] functional unit is the
nephron.
26
Normal Renal Static Imaging

27
Abnormal Imaging
 1Abnormal Position Dimension and or
Morphology
Wandering kidney ,Congenital deformity ,
Pyelonephritis

 2 Abnormal Radioactive Distribution


Diffuse or localized defects (Occupying lesions) :tumor ,cyst etc.

 3. Non-visualization:
Renal nonfunction or congenital single kidney.

[Link] radioactivity in the localization:


Congenital anomalies, Locally inpatent drainage
28
Horseshoe Kidney

29
Right Kidney Atrophy

Shown in the patients with the pyelonephritis .


30
Dynamic Renal Imaging
 2.1 Principle
The use of tracers,which are taken up and
excreted by the kidney,allows the estimation
of renal perfusion, divided, drainage and
assessment of the lower urinary tract.

31
Radiopharmaceuticals
2.1.1 Glomerular filtration:
99mTc-DTPA ,99m Tc-TTHA, 99m Tc-PAHIDA ,etc
2.1.2 Renal tubular epithelial secretion:
131I-OIH, 99mTc-EC, 99mTc-MAG 99mTc-DADS,
3,
99mTc-CO -DADS, etc.)
2

32
Procedure
 Renal vasodilator not used in the past one
week.
 Rapid injection of a bolus.
 Posterior acquisition
 perfusion phase: 1f/s(30-60s)
 function phase: 1f/20-30s(20-30min)

33
Analysis
 Perfusion phase
 normal

 9-15s,abdominal aorta shown

 2 - 3 s later , both kidneys shown at the


same time with the same concentration.
 abnormal

 delayed imaging

 radiopharmaceuticals not evenly distributed.

34
Analysis
 Function phase
 normal
 within 2-4min, concentration
 4-6min later, elimination

 abnormal
 Ischemia
 obstruction

35
Analysis
 GFR: 125 + 25ml/min
 ERPF: 580 + 80ml/min

36
Functional Renal Imaging

 Radionuclide imaging with 99mTc-labeled agents


provides anatomic, functional, and collecting system patency
information. Imaging may be adequately performed in most
patients by using either 99mTc-MAG or99mTc-DTPA.
3

37
 For convenience of interpretation and reporting,functional
imaging of the kidneys may be divided into three phases:
blood flow, parenchymal uptake and excretion, and
collecting system patency. Normally, both kidneys can easily
be imaged on a standard or large field-of-view gamma
camera with a parallel-hole collimator. Image information is
usually collected in digital dynamic mode or on an interfaced
computer and reformatted in temporal sequences that reflect
both initial renal perfusion and subsequent function.
38
Renal Perfusion Phase

 Evaluation of renal blood flow and function of native


kidneys is performed from the posterior projection,
whereas the evaluation of transplant blood flow and
function is performed from the anterior projection.
Normally, a small bolus of high-activity (10 mCi [370
MBq]) 99mTc-labeled radiopharmaceutical (99mTc-DTPA
or 99mTc-MAG3) is injected intravenously, preferably
into a large antecubital vein.

39
 Imaging renal perfusion is usually begun as the bolus is
visualized in the proximal abdominal aorta, with
subsequent serial images made every 1 to 5 seconds,
depending on the instrumentation available and the
preferences of the interpreter.

40
Normal Renal Blood Flow. A bolus of 99mTc-DTPA in the lungs is visualized at the
top of the serial images at 1 second. By 3 seconds, the aorta is fully visualized. By
5 to 6 seconds, both kidneys are clearly seen. The flow is symmetric to both
kidneys. Note that in normal perfusion, the activity seen in the kidneys is about
equal to that seen in the aorta just above the aortic bifurcation. Maximal activity
in the kidneys usually is reached later, between 30 and 60 seconds.
41
 The activity reaches the kidneys about 1second after the
bolus in the abdominal aorta passes the renal arteries. Time-
activity curves reflecting renal perfusion during the first
minute may be generated by drawing regions of interest over
the aorta and each kidney. Each of the renal curves may then
be compared with the time-activity curve of the abdominal
aorta to assess relative renal perfusion.

42
 Occasionally, the spleen overlies the left kidney, giving a
false impression of asymmetrically increased left renal
perfusion or of a “phantom kidney” in patients with prior
left nephrectomy. With the exception of renal transplant
evaluation, the renal perfusion phase is thought by some to
contribute the least to functional assessment and may be
omitted as appropriate, allowing smaller administered activity
to be used and reducing patient radiation dose.

43
Renal Perfusion Imaging
Posterior view.
Blood flow 3-second
frames show prompt
Celiac perfusion to both
artery
kidneys.
The immediate
blood pool image
shows radiotracer in
the liver,spleen
heart and lung,as
well as the kineys.

44
Renal Perfusion Imaging
Posterior view.
Blood flow 3-
second frames
show prompt
perfusion to both
kidneys.
The immediate
blood pool image
shows radiotracer
in the liver,spleen
heart and lung,as
well as the kineys.

45
Renal Parenchymal Function Phase

 Renal parenchymal function imaging consists of dynamic or


sequential static acquisition of 3- to 5-minute 99mTc-DTPA or
99mTc-MAG images over 20 to 30 minutes.
3

 Image evaluation includes attention to renal anatomy and


position and adequacy of function gauged by parenchymal
uptake and initial clearance, including relative renal symmetry.

46
 These are assessed both visually and by inspection of time-
activity (renogram) curves generated from regions of interest
placed over the cortex of each kidney, as discussed below.
With 99mTc-MAG3, the maximal parenchymal activity is seen
at 3 to 5 minutes, with activity usually appearing in the
collecting system and bladder by about 4 to 8 minutes.

47
Normal Renogram.
After administration of
technetium-99m mertiatide
(MAG3), maximal kidney activity
is seen at about 3 to 5 minutes,
and by 4 to 5 minutes, the
bladder can be identified at the
bottom of the images. By about 8
to 12 minutes, most of the
activity has cleared the
parenchyma and is seen in the
collecting systems, making the
kidneys appear slightly smaller
48
than on the early images.
Functional Imaging
Kidneys are visualized
clearly at 2-4min normal
position, dimension,and
morphology,homogenous
distribution.
The distance ureters are
never well visualized.
Renal and background
clearance is
prompt,consistent with
good renal function.
Renal complete clearance is
in 20 minutes.

49
(region of interest,ROI)was applicated to
obtain the time-activity curve,renogram

50
Function Imaging

51
 1min,a little tracer
shown in the kidneys
 2-4min:cortical
uptake is maximum.
 3-5min: calyx and
pelvis are visualized.
 3-4min:bladder are
visualized.
 9-10min : clearance
of kidney cortex are
visualized.
 15-20min:complete
clearance.

52
Collecting System Phase
 Overlapping with the excretion phase of the study,
assessment of collecting system patency is an integral part of
overall urinary functional assessment. Some laboratories
routinely administer the diuretic furosemide (Lasix) to
facilitate transit of activity from the renal pelvis and ureters to
the bladder and to exclude any significant mechanical
obstruction. Postvoid or postambulation images to enhance
collecting system drainage may also be obtained as needed.

53
Renal Cortical Scintigraphy
 3.1 Radiopharmaceuticals
 99mTc-DMSA: is used for high resolution imaging of the
renal [Link] agent is slowly cleared from the blood
as a result of its high protein [Link] 4% is
extracted per [Link] localizes to the renal cortex by
binding to sulfhydryl groups proximal renal tubules.

54
Clinical Indications
 4.1 Renal Artery Stenosis狭窄
Renal artery stenosis may be recognized by its effect on the
inflow into and subsequent reduced function of the affected
[Link] is enhanced by prior administration of angiotensin
converting enzyme [Link] technique is useful not only
for screening,but also for monitoring the effect of
function,rather than the anatomical lesions shown by
conventional imaging,which may not be associated with
significant change.
55
Renal Artery Stenosis

The left kidney(L) exhibits normal uptake and clearance ,whereas the right
kidney(R) has poorly uptake and clearance. 56
•Right Renal Artery Stenosis

57
Captopril Test

 Renal artery stenosis


may be recognized
by its effect on the
inflow into and
subsequent reduced
function of the
affected kidney.

58
R L

• Dynamic Renal imaging of Left Renal Artery Stenosis


(a.Taken Captoprils [Link] Dynamic Renal Imaging )
59
4.2 Infection
 Particularly in paediatric patients,functional disturbance in
renal parenchyma with prognostic significance(often a prelude
to scarring in children with reflux) may be demonstrated with
99mTc-DMSA scanning and prompt decisions regarding
[Link] in children may be asssessed by
direct(activity introduced into the bladder via catheter) or
indirect(99mTc-MAG3 excreted by kidney) cystography. This
has a radiation dose advantage on the X-ray technique.

60
Acute nephropyelitis (cicatrix)

61
4.3 Obstruction

Dilated renal collecting systems may not be obstructed


(normal function,good prognosis).
Interventional decisions may be assisted by the diuretic
renogram which uses a rapidly cleared radiopharmaceutical
to fill,then stress the dilated
system with [Link] dilated,but not obstruct-
ed system,clears promptly(typically half-clearance
time<13min).
62
Right uronephrosis 63
64
Left uronephrosis 65
Left uronephrosis 66
Left ureter obstruction
67
4.4 Transplant
In the early post-operative period,perfusion to the
transplant may be [Link] tubular necrosis
is usual and rapid fading of filtered tracer will occur
without [Link] leaks or obstruction may
also be diagnosed and differentiated from lymphocele.
Later,serial studies may be used to monitor rejection.

68
N or ma l
R e n a l
Transplant

69
Review
Renogram :
Normal curve
Seven types of abnormal curve
Prabola type
Low level prolonged type
Low level descending type
Acute rising type
High level prolonged type
Stepwise drop type
Small kidney type
Clinical applicance of dynamic renal imaging
70
Thank you!

71
Cardiovascular System
ANATOMY AND PHYSIOLOGY
ANATOMY AND PHYSIOLOGY

The volume-pressure diagram Left ventricular volume over one cardiac cycle
ANATOMY AND PHYSIOLOGY
SPECT Myocardial Perfusion Imaging
Images of flow distribution throughout the myocardium

Administering a radiopharmaceutical whose distributes in the myocardium is associated with

regional coronary artery perfusion

Taking a snapshot of with regional coronary artery perfusion


6
Myocardial Perfusion Imaging
Radiopharmaceuticals
Conventional and Dedicated Cardiac SPECT and SPECT/CT
Imaging Protocols
Myocardial SPECT Image Processing and Display
Image Interpretation
SPECT With Gated Acquisition (G-SPECT)
Patient Stress Protocols
Clinical Applications of Myocardial Perfusion Imaging
Myocardial Perfusion Imaging
Radiopharmaceuticals

Advantages of Tc-99m
Ready availability

Larger administered activity

Lower radiation doses

Photon energy of 140 keV


Myocardial Perfusion Imaging
To determine the adequacy of blood flow to the

myocardium

Exercise or pharmacologic stress

EEG Gating (G-SPECT)


Imaging Protocols of
Myocardial Perfusion Imaging
SPECT with gated acquisition

Differing significantly depending on


◦ Radiopharmaceutical

◦ Instrumentation

◦ Exercise or pharmacologic stress

One-Day Rest–Stress Protocol

Two-Day Protocol

Stress-Only Protocol
Exercise Protocols in
Myocardial Perfusion Imaging
The classic mode of stress 50% Submaximal stress
A multistage treadmill exercise test
◦ Bruce protocol • Reasons to Terminate Cardiac Stress Tests
◦ Modified Bruce protocol
Stationary bicycle exercise
ECG and blood pressure monitored
Radiopharmaceutical injected at peak stress
Peak stress varies with the institution
◦ Chest pain
◦ Significant ECG changes appear
◦ Heart rate reaches 85% of age-related predicted
maximum heart rate (220-age)
◦ Heart rate blood pressure product > 25,000
Pharmacologic Stress in
Myocardial Perfusion Imaging
Pharmacologic Stress Agents

An excellent alternative

Pharmacologic stress agents

◦ Nonnitrate vasodilators: Regadenoson (Lexiscan),

Adenosine, and Dipyridamole (Persantine)

◦ Inotropic drug: Dobutamine


SPECT Myocardial Perfusion Imaging

Relationship of coronary blood flow at exercise (peak blood flow) and rest (basal blood flow) relative to the percentage
diameter of coronary artery stenosis (diameter narrowing).
Image Processing and Display of
Myocardial Perfusion Imaging
Three planes
◦ Short-axis

◦ Vertical long-axis (VLA)

◦ Horizontal long-axis (HLA)


Image Processing and Display of
Myocardial Perfusion Imaging

Normal SPECT Technetium-99m Sestamibi Stress–Rest images Normal Polar (Bull’s Eye) Display
Patterns of abnormal distribution
in Myocardial Perfusion Imaging
Reversible (transient) defects
◦ Stress-induced ischemia

Nonreversible (fixed) defects Reversible (Transient) Defects

◦ Permanent myocardial damage

◦ Indicating areas of scarring or fibrosis

Reverse perfusion defects

Nonreversible (fixed) defects


Patterns of abnormal distribution
in Myocardial Perfusion Imaging
Reversible (transient) defects
◦ Stress-induced ischemia

Nonreversible (fixed) defects

◦ Permanent myocardial damage

◦ Indicating areas of scarring or fibrosis

Reverse perfusion defects

Reverse perfusion defects


G-SPECT Myocardial Perfusion Imaging
ECG Gating (G-SPECT) : LV wall motion and LV function

ECG Gating SPECT


G-SPECT Myocardial Perfusion Imaging
Better isolate the structures of interest and allow more accurate assessment of motion in specific wall
segments and calculation of individual chamber functional parameters

Advantages of ECG Gating (G-SPECT)


◦ Identification of suspected attenuation artifacts

◦ Enhancing detection of multivessel CAD (Coronary Artery Disease)

◦ Performing risk assessment of patients with known or suspected CAD

◦ Assessment of myocardial viability

◦ Performing follow-up of patients undergoing revascularization procedures to assess any LV wall motion improvement

◦ Distinguishing ischemic from nonischemic cardiomyopathy


Clinical Applications of
Myocardial Perfusion Imaging
Diagnosis of Coronary Artery Disease (CAD)
Prognosis and Risk Stratification in CAD
Hemodynamic Significance of Coronary Stenosis
Evaluation of Myocardial Revascularization
Risk Stratification After Myocardial Infarction
Myocardial Viability Determination
Evaluation of Acute Chest Pain
Preoperative Risk Assessment for Noncardiac Surgery
Diagnosis of Coronary Artery Disease Sensitivity and Specificity of Tests for Obstructive
Coronary Artery Disease
Indication
◦ Routine exercise ECG test is nondiagnostic

◦ Intermediate probability of disease

Perfusion defects in more than one vessel distribution


strongly indicates the presence of two- or three-vessel
disease

A perfusion defect present in the distribution of only one


vessel cannot be used to exclude the involvement of other
vessels
G-SPECT on Diagnosis of Coronary Artery
Disease
G-SPECT on Diagnosis of Coronary Artery Disease

Assessing the severity of CAD using G-SPECT

Differentiating a true fixed perfusion defect from artifact

Improves the detection of multivessel CAD

Distinguishes between patients with ischemic and nonischemic cardiomyopathy


Case 1
FEMALE, 67Y,ST GOING DOWN ON ECG

24
25
26
27
Case 2
ST GOING DOWN ON ECG

28
29
30
31
Prognosis and Risk Stratification in CAD
Identifying patients with CAD at risk for cardiac death
for revascularization

G-SPECT signs for high mortality rate


◦ Post-stress LVEF < 45%

◦ End-systolic volume (ESV) > 70 mL


Hemodynamic Significance of Coronary
Stenosis
MPI measuring hemodynamics

Arteriography measuring anatomy

Diameter narrowing >50%

G-SPECT
◦ Stress-induced wall motion abnormalities confer high specificity for coronary stenoses greater than 70%
Evaluation of Myocardial
Revascularization
Identifying patients with CAD at risk for cardiac death
for revascularization

G-SPECT
◦ Improvement in global LV function (LVEF) or regional wall
motion after the procedure
Risk Stratification After Myocardial
Infarction
High risk
◦ Significant residual peri-infarct ischemia

◦ Ischemia remote from the acute injury

G-SPECT
◦ Predictor of future adverse cardiac events
Myocardial Viability Determination
Indication for Revascularization
◦ Distinguishing fixed perfusion defects caused by nonfunctional
salvageable myocardium or myocardial scar

Viable dysfunctional myocardial segments with 99mTc sestamibi


uptake higher than 50%-60% of maximal regional uptake

Nonviable myocardium with uptake less than 30%

G-SPECT
◦ Detectable wall motion and/or wall thickening improves
Evaluation of Acute Chest Pain
Maybe negative on ECG, and cardiac biomarker

Differentiating unstable angina pectoris from acute

myocardial infarction
Preoperative Risk Assessment for
Noncardiac Surgery
Evaluating cardiac status before high-risk, noncardiac

surgical procedures

◦ Number and extent of reversible myocardial perfusion

defects
PET CARDIAC IMAGING Advantages of PET Perfusion Imaging

High diagnostic accuracy—High sensitivity and


PET Myocardial Perfusion Imaging specificity for multivessel CAD
Radiation exposure—Somewhat lower than most
other radiation-based cardiac assessments
PET Myocardial Viability Imaging
Consistent high-quality images
Short acquisition protocols
Myocardial blood flow quantification at rest and stress
Cardiac Positron Radiopharmaceuticals
Strong prognostic power for risk stratification in
multiple patient populations
Allows detection of coronary artery calcification
Indications for PET Myocardial Perfusion
Imaging
(“First-Line Test”)

Patients meeting the criteria for cardiac stress imaging who are unable to complete a diagnostic-level exercise
stress

(Patients who meet appropriate criteria for a stress imaging test who also meet one of the conditions below)

Inconclusive, poor quality, or discordant prior

Inconclusive, poor quality, or discordant prior stress imaging studies

Patient body characteristic preventing conclusive stress imaging by other techniques

High-risk patients in whom diagnostic accuracy has greater clinical implications

Young patients with anticipated repeat examinations adding to lifetime radiation exposure

Patients in whom absolute myocardial blood flow measurements are clinically important
PET Myocardial Perfusion Imaging
Rubidium-82 Chloride Protocol for Myocardial
Perfusion
◦ Rb-82 is transported through the Na+/K ATPase
pump

◦ Short Half-life

◦ 20-60 mCi

◦ Pharmacologic stress is used instead of exercise

Rubidium-82 ( 82Rb) Gated PET/CT


PET Myocardial Perfusion Imaging
Rb-82 stress myocardial perfusion study

Perfusion defects seen after pharmacological


stress that normalize on rest studies suggest
ischemia
PET Myocardial Perfusion Imaging
Nitrogen-13 Ammonia Protocol for Myocardial Perfusion Imaging
◦ Taken by myocardium, brain, liver, and kidney

◦ Be converted to N-13 glutamine

◦ Half-life ≈10 minutes

◦ Requiring onsite cyclotron production)

◦ Decays 100% by positron (beta+) emission

◦ Technique
◦ 10-20 mCi

◦ Imaging starts at 4 min after injection


PET Myocardial Perfusion Imaging

N-13 ammonia myocardial perfusion scintigraphy in


severe multivessel ischemia
PET Myocardial Viability Imaging
18F-Fluorodeoxyglucose Imaging Protocol
◦ Fasting for 6 to 8 hours

◦ Oral glucose loading (25–100 g)

◦ IV administration of 10 to 15 mCi of 18F-FDG after 1-


2 hours

◦ Imaging after IV injection


PET Myocardial Viability Imaging
Myocardial viability assessment entails combined resting perfusion and 18F-FDG images

Hibernating Myocardium
Normal myocardium gets energy (Fasting):
◦ Long-chain fatty acids 70%
◦ Glucose 20%

Ischemic myocardium gets energy:


◦ Long-chain fatty acids reduced markedly
◦ Greater anaerobic metabolism of glucose

Mismatched myocardial perfusion


◦ FDG uptake greater in severely hypoperfused than that in the remainder
PET Myocardial Viability Imaging
Mismatched myocardial perfusion

Mismatched myocardial perfusion. Images above are


resting Rb-82 and images below are F-18- FDG. There is
a perfusion metabolic mismatch in the anterior, septal,
and apical walls. ANT, Anterior; INF, inferior; LAT, lateral;
SEP, septal.
PET Myocardial Viability Imaging
Negative for hibernating myocardium

Rb-82 myocardial perfusion stress (above), rest (middle),


and F-18 FDG (below) with matching defects consistent
with myocardial infarction and nonviable myocardium.
PET Myocardial Viability Imaging
Diagnostic Patterns: Positron Emission Tomography Metabolic and Perfusion Imaging
Radionuclide Imaging Of Cardiac Function
G-SPECT
◦ most frequently performed isotopic evaluation

Equilibrium blood pool ventriculography (E-BPV)


◦ Gated blood pool ventriculography

◦ Multigated acquisition (MUGA)

First-pass or first-transit radionuclide angiography (FP-RNA)


◦ Rarely used now
Radionuclide Imaging Of Cardiac Function
Quantitative Data
◦ Systolic Function: LVEF (left ventricle ejection fraction)

◦ Diastolic Function: PFR (peak filling rate)

Qualitative Data
Gated Cardiac Equilibrium Blood Pool
Imaging Visual Data Analysis
谢谢!
Nuclear Medicine of Central
Nervous System
Nuclear Medicine of
Central Nervous System
OUTLINE

 Radionuclide Brain Imaging


 Planar Brain Perfusion Imaging
 SPECT and PET Brain Imaging
 Clinical Applications

 Cerebrospinal Fluid Imaging


 Radiopharmaceuticals and Technique
 Normal Examination
 Clinical Applications
RADIONUCLIDE BRAIN IMAGING

 Planar Brain Perfusion Imaging

 SPECT Brain Imaging:


 Perfusion

 PET Brain Imaging


 Metabolism imaging

 Receptor imaging

 CSF Imaging

 Clinical Applications
Planar Brain Perfusion Imaging

 Dynamic or angiographic study


 Rapid sequential images of the arrival of the
radioactive bolus in the cerebral hemispheres
 Qualitative measure of regional brain perfusion

 Delayed static images


 The most common application of planar technique
is in the setting of suspected brain death
Planar Brain Perfusion Imaging

 Perfusion Agent
 99mTc-DTPA, 99mTc-pertechnetate
 99mTc-HMPAO, 99mTc-ECD
Normal Planar Brain
Scan
Normal Anterior Radionuclide
Angiogram(99mTc-DTPA)
Normal Planar Brain
Scan
Normal Planar Static Brain Scan(99mTc-
DTPA)
Normal Perfusion Images
99mTc-HMPAO
SPECT Brain Imaging

 Lipophilic Radiopharmaceuticals
 Cross the intact blood-brain barrier
 Retained by the braintissue in proportion to regional cerebral
blood flow
 99mTc-HMPAO
 Rapid first-pass uptake
 5% localizing within bran
 99mTc-ECD
 More statble
99mTc-ECD SPECT Brain Perfusion
99mTc-ECD SPECT Brain Perfusion
Abnormal Signs of Perfusion
Imaging
•Viable on two dimensional images at
least (>2×2cm)
•Enlargement of ventricles or area of
white matter
•Widen distance between caudate nuclei
•Unsymmetrical thalami, caudate nuclei
or cerebellum

13
PET Brain Perfusion Imaging
PET Brain Perfusion Imaging
PET Brain Perfusion Imaging
PET Brain Imaging

 18F-FDG
 Most common radiopharmaceutical for PET Brain
imaging
 Situation of regional glucose metabolism
 Kept in silent and darkened room
18F-FDG

18
FDG 代谢
Normal 18F-FDG PET Brain Scan
Normal 18F-FDG PET Brain Scan
Abnormal Signs

1. Decreased radiation or defect


2. Increased radiation
3. Enlargement of White Matter
4. Disarrangement of anatomic stuctures
5. Abnormal distribution of radiation
6. Atrophy
7. Asymmetric distribution of radiation

22
Clinical Applications

1. Brain Death
2. Cerebral Infarction
3. Transient Ischemic Attack
4. Brain Tumors
5. Localization of Epilepsy Lesion
6. Alzheimer Disease

23
Clinical Applications

 Brain Death
 By the presence or absence of intracerebral
perfusion
 Planar radionuclide angiogram using 99mTc-DTPA
or 99mTc-pertechnetate
 SPECT brain perfusion imaging using 99mTc-ECD
and -HMPAO
Indications for Confirmatory Radionuclide Brain
Death Assessment

• If components of neurologic examination cannot be performed

• If uncertain neurologic examination result is present

• If apnea test cannot be performed

• To shorten duration of observation period

• If uncertain medication effect is present

• If helpful for family members to better comprehend diagnosis


If clinical evaluation of the patient suggests
brain death and no cerebral perfusion is
demonstrated on the radionuclide study, brain
death is virtually certain.

2020/11/30
Cerebral Infarction

• Sensitivity
• 20% on CT 8h after cerebral infarction
• 90% on SPECT brain perfusion imaging 8h after
cerebral infarction
• Similar on both by 72h

• MRI: Best technique

2020/11/30
Acute and Chronic Cerebral Infarcts

99mTc-HMPAO SPECT
Acute Cerebral Infarcts

29
Subacute Phase of Cerebral Infarcts

99mTc-HMPAO SPECT
Transient Ischemic Attack

• Differentiated by SPECT within 6 hours of symptom onset

• 60% viable on SPECT in the first 24 hours

• >40% detected on SPECT 1 week after the insult

• PET is more reliable within 5-8 hours


Brain Tumors

• Localized defects on SPECT brain perfusion (dead technique)

• Maybe valuable in distinguishing between radiation necrosis and


tumor recurrence in conjunction with thallium-201 (201Tl)
Tc-HMPAO

Tl-201

Recurrent Brain Tumor


Brain Tumors

• PET/CT plays a role in the evaluation of brain malignancies

• The degree of 18F-FDG uptake in primary brain tumors generally


correlates inversely with patient survival

• FDG PET imaging is limited on low-grade tumors

• High FDG uptake in a tumor previously known to be low grade is


likely to represent anaplastic transformation

• Lymphoma is typically very hypermetabolic

• In differentiating recurrent tumor from radiation necrosis


Central Nervous
System Metastatic
Disease from Lung
Cancer on FDG
PET/CT

2020/11/30
Central Nervous
System Metastatic
Disease from Lung
Cancer on FDG
PET/CT

2020/11/30
Pituitary Adenoma on PET

18F-FDG PET

2020/11/30
Glioma on PET

38
Glioma on PET

39
Recurrent Glioma on PET vs MRI
Radiation Necrosis on FDG
PET vs MRI
Mengioma on SPECT Perfusion
Glioma on SPECT Perfusion
Epilepsy

• PET and SPECT can play a significant role in noninvasively


localizing epileptogenic foci before surgery when lesions are not
visible on preoperative MRI or visualized lesions do not correlate
with electrophysiological data and/ or clinical assessment
• Especially pertinent in children younger than 2 years
• 70% of patients undergoing partial temporal lobectomy
experience amelioration or eradication of seizures
• Imaging Methods
• 99mTc-ECD or HMPAO perfusion
• FDG PET

6 months
Ictal Imaging for Temporal Lobe Epilepsy

• Most sensitive procedure for the identification of seizure foci

• During the seizure or within 30 seconds after its completion to


document this increased perfusion and localize the epileptogenic
focus

• 99mTc-HMPAO or 99mTc-ECD brain perfusion: Epileptogenic


foci appear as areas of increased activity
Ictal Imaging for Temporal Lobe Epilepsy

• Epilepsy (Interictal
Study)
• Axial and coronal
99mTc-HMPAO brain
perfusion images
obtained between
seizures show
characteristically
decreased activity in the
right temporal lobe
Ictal Imaging for Temporal Lobe Epilepsy

• FDG PET: Usually not technically feasible

Epilepsy (Ictal Study)


Epilepsy Interictal PET/MRI Study.

MR T WI 18F-FDG
Epilepsy Interictal PET/MRI Study
Alzheimer Disease(AD)

• Perfusion defects symmetrically in the bilateral posterior temporal


and parietal cortices, the precuneus, and the posterior cingulate
gyri with a positive predictive value of more than 75% to 80%
• Asymmetrically in approximately 30% of patients
• Brain perfusion images using 99mTc-HMPAO or 99mTc-ECD
AD

99mTc-HMPAO SPECT
AD

FDG PET
Development of
AD
Deposition of senile plaques

• β-amyloid plaques

• Insoluble aggregates of β-

amyloid protein

• Neurofibrillary tangles (NFTs)

• Aggregates of hyper-

phosphorylated tau protein


Amyloid Imaging on AD

Normal

AD
Amyloid VS FDG Imaging
[11C]PIB-PET images
18F-BAY94-9172
(Aβ ligand) PET images
Parkinson’s Disease

• Neurons in the substantia nigra destroyed


• Prototypic movement disorder
• Inexorably progress over time
• Constellation of motor
• Slowness of movement
• Muscular rigidity
• Tremor
• Postural instability
• Nonmotor symptoms
• Cognitive dysfunction
• Psychiatric features
Parkinson’s Disease

• 18F-FDOPA-PET • 18F-FP-CIT-PET
Cerebrospinal Fluid Imaging

• Cisternography
• 111In-DTPA:sufficient long half-life for its use in the functional study of
CSF dynamics

• Alternating 1ml of CSF with 1ml agent

• Planar images of the skull (anterior, posterior, and lateral

• views) are acquired with a gamma camera at 2, 6, 24, and 48 h

• Positive scan if activity outside expected location of CSF

• SPECT may increase sensitivity


Cisternography

111In-DTPA Cisternography at 3h and 24h


Cisternography: Rhinorrhea

Assessing CSF leakage,


such as rhinorrhea and/
or otorrhea
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Oncologic Imaging of Nuclear


Medicine
Jiacheng Liu
Department of Nuclear Medicine
Zhongda Hospital, Southeast University
Jiachengliu@[Link]

厚德精业 敦行至善

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Outline

• 18F-FDG PET Imaging

• Other PET Radionuclides

• Targeted Tumor Imaging

• Nonspecific Tumor Imaging

• Lymphoscintigraphy

1
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

18F-FDG PET Imaging

• Indications

• Patient Preparation for 18F-FDG Imaging

• Normal 18F-FDG Distribution and Variants

• Qualitative Image Interpretation

• PET Image Quantitation

• Whole-Body 18F-FDG PET/CT Neoplasm Imaging

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

PET CT Scanner

GE Optima CT660

Double-digit sensitivity
Q Suite

2
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

• Correction for PET images


• Denoising
• Alternating standard
correction source
• Short half-life isotopes
• Localizing radiation
source
• More accuracy
• Identifying physiological
uptake
• Detecting small lesion
• Additional imformation

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

18F-FDG Levels in Various Normal Tissues

3
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Metabolism of FDG

FDG in Cancer Cells

[Link] [Link]

4
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

PET Image Quantitation


• MRGlu:Metabolic Rate of Glucose

• SUV :Standardized Uptake Value

• SUVmax
• Calculations from the hottest pixel in the region of interest
• SUVpeak
• Average SUV in a small volume around the hottest voxels (1-ml
OR 1.2-cm diameter)
• SUVmean
• An average value of all pixels in the ROI
• SUVmax-N
• Averaging SUV from several hottest voxels(5-10)

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Accumulation of 18F-FDG in Malignancies

5
2020/12/10

Indications of PET-CT [Link] 东南大学附属中大医院核医学科


Department of Nuclear Medicine Zhong Da Hospital Southeast University

 Acute myeloid leukemia


 Merkel cell carcinoma
 Ampullary cancer
 Mesothelioma
 Anal cancer
 Multiple myeloma and plasmacytomas
 Appendiceal cancer
 Neuroendocrine tumors
 Brain tumors
 Non‐Hodgkin's lymphoma
 Breast cancer
 Non‐small cell lung carcinoma
 Burkitt's lymphoma
 Occult primary cancers
 Castleman's disease
 Ovarian cancer
 Cervical cancer
 Pancreatic cancer
 Chordoma
 Paraneoplastic syndrome
 Chronic lymphocytic leukemia/small lymphocytic
 Penile cancer
lymphoma (CLL/SLL) with suspected Richter's
 Post‐transplant lymphoproliferative disorder
transformation
 Primary cutaneous B‐cell lymphoma
 Colorectal cancer
 Primary peritoneal cancer
 Diffuse large B‐cell lymphoma (DLBCL)
 Small cell lung carcinoma
 Esophageal cancer
 Small bowel adenocarcinoma
 Ewing sarcoma and osteosarcoma
 Soft tissue sarcoma
 Fallopian tube cancer
 Solitary pulmonary nodules
 Follicular lymphoma
 T‐cell lymphoma (includes peripheral T‐cell
 Gastric cancer
lymphoma, Mycosis Fungoides/Sézary
 Gastrointestinal stromal tumors
Syndrome, primary cutaneous CD30+ T‐cell
 Head and neck cancers (excluding cancers of the
lymphoproliferative disorders)
central nervous system)
 Testicular cancer
 Hodgkin lymphoma
 Thymic malignancies
 Mantle cell lymphoma
 Thyroid cancer
 Marginal Zone and MALT lymphoma
 Vaginal cancer
 Melanoma

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

The image features of Tumors on PET/CT

• Lung Cancer

• Breast Cancer

• Lymphoma

• Esophageal Cancer

• Gastric Cancer

• Colon Cancer

• Tumors in Head and Neck

6
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Lung Cancer

肺癌伴纵隔淋巴结转移

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Breast Cancer

7
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Breast Cancer

Breast cancer with lymphatic


metastases in axillary fossa

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Breast Cancer

Metastases in Liver

8
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Gastric Cancer

Colon Cancer

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Colon Cancer

9
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Nasopharyngeal Carcinoma

Thyroid carcinoma

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Clinical Application of PET/CT on Tumors

1. Diagnosis and differentiation of Tumors


2. Staging tumors
3. Follow-up and Monitoring
• Evaluation of therapeutic efficiency
• Monitoring
• Prediction of Outcoming
4. Seeking the original lesion
5. Fever of unknown origin
6. Screening for Tumors
7. Localization of tumor

10
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

1. Diagnosis and differentiation of


Tumors

Diagnosis

Male Chronic Gatritis


5 CT and 2 CTA:
Embolism of right
pulmonary artery

Malignant embolus

11
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

PET/CT Lymphoma
Pathology NK/T lymphoma

Fever for 2 Months

SUVmax>20

B-cell Lymphoma

Female,76y , 37.6

Bone marrow aspiration

12
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

CT:nodule is possible
Lung Adenocarcinoma;
StageⅠA3(T1a,N0,M0)

MRI Vs PET‐CT on low‐differentiation liver cancer 东南大学附属中大医院核医学科


Department of Nuclear Medicine Zhong Da Hospital Southeast University

18F‐FDG PET‐CT

Malignant node –red Malignant node –red


Liver tissue‐red Liver tissue‐red

Hectors, et al. Contrast Media & Molecular Imaging. Vol2018, Aricle ID 5638283

13
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University
18F‐FDG PET‐CT Liver Mass and Cancer Embolus in Portal Vein

Shah, et al. In Clinicians’ Guides to Radionuclide Hybrid Imaging. Springer, 2014

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

2 Staging

14
2020/12/10

国家卫生健康委: 东南大学附属中大医院核医学科
18个肿瘤诊疗规范(2018年版)结肠癌(2015年版)
Department of Nuclear Medicine Zhong Da Hospital Southeast University

• “PET-CT:目前是除惰性淋巴瘤外,淋巴瘤分期与再分期、疗效评价和预后预测的最佳检查方法”
• “PET-CT是肺癌诊断、分期与再分期、疗效评价和预后评估的最佳方法”
• (黑色素瘤)“经济情况好的患者可行全身PET-CT检查,特别是原发灶不明的患者。PET是一种更容易发现亚临
床转移灶的检查方法”
• “治疗前PET-CT显像有助于卵巢癌良恶性的鉴别诊断,有利于发现隐匿的转移灶,使分期更准确”
• (胰腺癌)“正电子发射计算机断层成像(PET-CT):显示肿瘤的代谢活性和代谢负荷,在发现胰外转移,评
价全身肿瘤负荷方面具有明显优势”
• 食管癌、胃癌、甲状腺癌:转移、分期;
• 结肠癌:“但对于病情复杂、常规检查无法明确诊断的患者可作为有效的辅助检查。术前检查提示为Ⅲ期以上肿
瘤,为了解有无远处转移,推荐使用”
• 子宫内膜癌:“可疑存在非常见部位的转移”,“病理提示为高级别肿瘤”
• 宫颈癌:“推荐有条件者使用PET-CT:① FIGO 分期为ⅠB1期及以上的初诊患者治疗前分期(包括ⅠB1期有保
留生育功能需求的患者);②因其他原因行单纯子宫切除术意外发现宫颈癌拟全身评估者;③拟行放射治疗需影
像辅助勾画靶区;④ FIGO 分期为ⅠB2期及以上或其他存在高危因素的患者治疗结束3~6个月后随访监测;⑤随
访过程中可疑出现复发转移的患者”
• 乳腺癌:“临床局部晚期、分子分型预后差、或有症状可疑存在远处转移的患者疗前分期”,“术后患者随访过
程中可疑出现局部复发或转移”,“对于鉴别复发和放射性纤维化,PET-CT较其他常规影像检查具有优势”
• 肾癌:“多项研究也表明PET-CT显像对肾癌的淋巴结转移和远处转移要优于传统影像检查方法,尤其在判断肾
癌骨转移或骨骼肌转移方面更具优势,而且能够通过葡萄糖代谢变化早期监测疗效、预测患者的预后情况”
• 膀胱癌:“PET-CT诊断淋巴结转移的准确率优于CT和MRI”
• 成人急淋:“纵隔疾病的疗效判断依赖胸部CT和PET-CT”
• NCCN肿瘤学临床实践指南、美国胸科医师协会(The American College of Chest Physicians,ACCP)临床实
践指南
[Link]

T staging: Extension of tumor

Node hided in atelectasis

15
2020/12/10

Colon Invaded

N Staging

• CT:
• Major Diameter >10mm
• Minor Diameter >8mm
• Low Sensitivity
• PET/CT
• High Accuracy
• 15% Unexpected

16
2020/12/10

肺癌,伴
淋巴结转

东南大学附属中大医院核医学科
Liver cancer with nodal metastases Department of Nuclear Medicine Zhong Da Hospital Southeast University

17
2020/12/10

东南大学附属中大医院核医学科
Liver cancer with nodal metastases Department of Nuclear Medicine Zhong Da Hospital Southeast University

(Continued)

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

18F‐FDG PET‐CT showed the embolus

18
2020/12/10

Bladder Cancer with


nodal metastases

M Staging

• PET/CT是评估远处转移最有效的方法
• 全身成像

• PET发现病灶,CT定位、形态学

• 骨转移,PET/CT优于骨扫描
• 假阳性和假阴性低

• 定位准确

19
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Staging:PET/CT Vs MRI

• MR:Brain
• FDG PET/CT lymphadenopathy, soft tissue, whole
body

20
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

3. Follow-up and Monitoring


• Evaluation of therapeutic efficiency

• Monitoring

• Prediction of Outcoming

东南大学附属中大医院核医学科
Therapeutic efficiency Department of Nuclear Medicine Zhong Da Hospital Southeast University

of surgical procedure, radiation and


chemotherapy
• High uptake of FDG in nontumor tissue
• Radiation: Inflammation, Granulomatous inflammation(2-3M)
• Chemotherapy:Reaction of bone marrow (2-3W)
• Surgical Therapy:post-procedure, Inflammation, Infection
• The window for PET/CT
• 2-3 M Post-radiation
• 2-3 W Post-chemotherapy
• Post-surgical procedure
• Advantages
• PET/CT VS CT、MR
• Visualizing cell activities (tumor, scar, necrosis)

21
2020/12/10

Lymphoma 东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Post-therapy Pre-therapy

东南大学附属中大医院核医学科
Brachyytherapy for lung cancer
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Post-therapy

22
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Brachytherapy for lung cancer(PET/CT VS CT+c)

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Brachytherapy for esophageal cancer(PET/CT VS CT+c)

23
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Brachytherapy for liver cancer(PET/CT VS CT+c)

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Brachytherapy for kidney cancer

24
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Brachytherapy for nodal metastasis(PET/CT VS CT+c)

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Brachytherapy for cancer in maxillary sinus (PET/CT VS CT+c)

25
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Brachytherapy for
osseous metastasis
(PET/CT VS CT+c)

Follow-up and monitoring

• Lung cancer
• CT+c report:
multiple cysts and
multiple metastases

PET/CT cysts

26
2020/12/10

Pancreatic carcinoma
Post-procedure

CA199:
5-15: 47.5U/ml
6-25: 125.1U/ml
7-4: 305.6U/ml

Negative on
US and CT

Prediction of Outcoming

• Berghmans et al. Meta-analysis : SUV is related outcoming of lung


cancer

• Xie et al. DLBCL-related Meta-analysis:SUVmax , MTV can prodict


progression-free survival (PFS) ,MTV may predict outcoming more
accuracy

• Pak et al. Meta-analysis:metabolic tumor volume (MTV) and total


lesion glycolysis (TLG) associated with outcoming
Berghmans T, et al. J Thorac Oncol, 2008, 3(1): 6-12
Hanin FX,et al. Eur J Cardiothorac Surg, 2008, 33(5): 819-823
Xie M, et al. Med Oncol. 2015;32(1):446
Par K, et al. J Nucl Med June 1, 2014 vol. 55 no. 6 884-890

27
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

4. Seeking the original lesion

Seeking the original lesion


• Larger field of view
• High sensitivity

28
2020/12/10

Seeking the original lesion

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Female 79 y
Ovary cancer with multiple
metastases

29
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

5 Fever of Unknown Origin

Facts affecting PET-CT features

• Disease Prevalence and Positivity

30
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Female, 22y Fever Hemophagocytic syndrome,HPS

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

6、Screening for Cancer

31
2020/12/10

Screening for Tumors

• Tumor biomarkers

• High risk population

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Screening

Increased CA199

32
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

7 Localization

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

PET/CT assisted for


biopsy

33
2020/12/10

PET/CT marking target


area for radiation

PET/CT marking target


area for radiation

34
2020/12/10

东南大学附属中大医院核医学科
Other PET Radionuclides
Department of Nuclear Medicine Zhong Da Hospital Southeast University

• 18F-Fluoride
• 11C- and 18F-Choline and 11C-Acetate
• 68Ga- and 18F-PMSA

Fatty Acid

11C-acetate 和18F-FDG PET/CT in Liver Cancer

35
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Fibrous Dysplasia of the Right First Rib

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

11C-choline and 18F-FDG PET/CT in prostatic cancer

36
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Targeted Tumor Imaging

• Neuropeptide Receptor Imaging


• Adrenal Tumor Imaging

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Neuropeptide Receptor Imaging

• Neuropeptides

• Consist of a few amino acids

• Synthesized and released by the brain, gut, endocrine system and lymphatic tissue

• Neuropeptides and receptors for imaging

37
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Somatostatin (Octreotide) Receptor Imaging

• Somatostatin: synthesized and released by endocrine and nerve cells


• Overexpression of somatostatin receptors occurs in numerous neuroendocrine
and some non-neuroendocrine tumors
• Neuroendocrine tumors :
• Derived from amine precursor uptake and decarboxylation (APUD) system cells
• Carcinoid, pituitary adenomas, pancreatic islet cell neoplasms, medullary carcinoma of
the thyroid, pheochromocytomas, neuroblastomas, paragangliomas, and small cell lung
cancers
• Radiolabeled analogs of somatostatin:
• 111In-labeled
pentetreotide (OctreoScan): Low hepatobiliary excretion (2%) and
gastrointestinal activity
• Imaging at 4 hours and again at 24 hours

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Normal 111In-Pentetreotide (Octreotide) Images

38
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Pulmonary Carcinoid

4 hours

24 hours

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Gastrinoma

39
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Adrenal Tumor Imaging

• Primary sympathoadrenal system tumors


• Pheochromocytomas
• Neuroblastomas
• Paragangliomas
• Iodine-123 or -131 MIBG
• Salivary glands
• Liver 3 hours
• Heart
• Thyroid gland.

Pheochromocytoma

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

NONSPECIFIC TUMOR IMAGING

• Gallium-67 Imaging

• Thallium-201 Chloride Imaging

• Technetium-99m Sestamibi Imaging

40
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Gallium-67 Imaging

• Gallium-67 citrate imaging

• Affinity for transferrin receptors on

tumor cells

• Be valuable for the diagnosis of

neoplastic disease

• Be supplanted by 18F-FDG PET/CT

Normal Gallium Scan at 48 hours

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Lymphoma on gallium scans

Scan at 48 hours

41
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Thallium-201 Chloride Imaging

• A potassium analog

• Imaging at 2-4 hours

• Distributed in skeletal muscle, myocardium, liver, spleen, stomach, and colon

• Applications:
• In distinguishing postradiation necrosis from recurrent brain tumor

• Acquired immunodeficiency syndrome-related neoplasms

• Low-grade lymphomas

• Replaced by PET

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Technetium-99m Sestamibi Tumor Imaging

• Lipophilicity: active uptake by mitochondria

• Distributed throughout whole body in proportion to blood flow


• Myocardium, thyroid, and salivary glands , spleen, kidneys, bladder, lungs, skeletal muscle,
liver, gallbladder, and small and large intestines

• Breast Cancer
• Contrast ratio of 6:1

• Homogeneous distribution in normal breast

• Rarely applied today

42
2020/12/10

东南大学附属中大医院核医学科
Application in Oncology: Sentinel
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Lymph Node Biopsy


• Lymphoscintigraphy:
• A procedure in which a small amount of radioactive colloidal tracer is injected into the
skin or other tissues of an organ and transported by the draining lymphatics to localize in
regional lymph node basins
• To determine the lymph node(s) receiving drainage and thus possibly
metastasizing tumor cells from the primary lesion
• Sentinel lymph node (SLN):
• The first lymph node (or nodes) on a direct lymphatic drainage pathway from a primary
tumor site
• The most likely location to harbor occult metastasis
• 99mTc-sulfur colloid (300 - 350 nm)
• 99mTc-tilmanocept: Bind macrophages and dendritic cells
• Taking serial 3- to 5-minute planar images up to 1 hour, and delayed images (2
to 4 hours)

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

Lymphoscintigraphy

43
2020/12/10

东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital Southeast University

谢谢!

厚德精业 敦行至善

44
Nuclear Medicine

2020.10.07

1
Nuclear Medicine
XIE YAN
Department of Nuclear Medicine,
Zhongda Hospital Southeast University

573358569@[Link]
83272058 83272148

2
What Is Nuclear Medicine?

Generally, this field encompasses any use of radioactive


materials in medicine. 3
4 4
SPECT/CT 5
PET/CT 6
Nuclear Medicine

★ Definition
• A branch of medicine is concerned with the use of
radioactive materials in the diagnosis and treatment of
disease and medical research. 7
Nuclear medicine specialists use safe, painless, and cost-
effective techniques to image and treat.

• Nuclear medicine imaging provides information about both


structure and function. 8
• Nuclear medicine imaging procedures often identify
abnormalities very early in the progress of a disease

9
prostate cancer, male
Nuclear medicine uses very small amounts of radioactive
materials (radiopharmaceuticals) to diagnose and treat
disease. 10
• In treatment, the radioactive materials
go directly to the organs being treated.

11
• The amount of radiation in a typical nuclear imaging procedure
is similar to that received during a diagnostic x-ray.
• The amount of radiation received in a typical treatment 12
procedure is kept within safe limits.
category:
basic nuclear medicine
clinical nuclear medicine

Content:
• Radionuclide imaging
• Function evaluation
• Radionuclide therapy
• In vitro methods (radioimmunoassay)

13
The history of nuclear medicine

14
Henri Becquerel (1852-1908)

In early 1896,
the French
physicist, Henri
Becquerel,
discovered that
a mysterious X-
ray was
produced by
uranium.

•1903 →Nobel Prize (physics) 15


Marie Sklodowska Curie (1867-1934)

• In 1897, Marie ( Marja Sklodowska)


became Becquerel's assistant and
took on the study of X-rays from
uranium as her doctoral thesis.
• Madame Curie called the
mysterious rays "radioactivity."
• polonium (Po-210) in honor of
Marie's birthplace, Poland.

16
The history of nuclear medicine
•1895 Wilhelm Roentgen →x ray
•1896 Henri Becquerel →uranium --x ray
•1898 Marie Curie → radium / polonium

•1901 Wilhelm Roentgen → Nobel Prize (physics)


•1903 Curie / Becquerel →Nobel Prize (physics)
•1911 Curie →Nobel Prize (chemistry)

17
•1899 Rutherford→half life,αandβparticle
–1908Nobel Prize (chemistry)
•1921 Albert Einstein → photoelectric effect
–Nobel Prize (physics)

18
•1934 Frederic Joliet-curie、
Elena Joliet- Curie
– Aluminium + α → 30P (T1/2 2min)
–Nobel Prize (chemistry)

19
Ernest Orlando Lawrence (1901-1958)

In 1929, Ernest O. Lawrence, working at the University of


California at Berkeley, invented the cyclotron .
1939 Nobel Prize in physics. 20
• 1937——technetium (99mTc);
1957 Generator

21
Radionuclides therapy

• 1901 radium —
tu berculose derma tosis
• 1938 32P — leukemia
• 1941 iodine(131I) —
hyperthyroidism
• 1946 iodine(131I) —
thyroid carcinoma

22
in vitro
In 1959, Yelow and
Berson
→radioimmunoassay

the concentration of
insulin in plasma.

1977 Nobel Prize


(medicine)

23
24
A brief history of the development of
nuclear medicine instruments

1950 Well type scintillation counter


Scintillation scanner
1951

1957 Gamma camera

PET Scintillation scanner


SPECT SPECT/CT PET/MR
PET/CT
1974
1979
2012
2001

25
25
abbreviation

ECT ——emission computed tomography

SPECT ——single photon emission


computed tomography

 PET ——positron emission tomography

26
• Nuclear physics

• Molecular nuclear medicine

27
• Atom→ protons + neutrons + electrons
• nucleus
• The number of protons in an atom is
called the atomic number and is
represented by the letter Z.
28
Terminology

nuclide
isotope
isomer
nuclide
• A nuclide is any individual atomic
species, characterized by a specific
number of protons , neutrons and
energy state.

• 131 I , 12 C
53 6
• 125 I , 131 I
53 53
• 99m Tc
43 ,
99 Tc
43 30
isotope

• The isotopes of an element are having


the same protons but different neutrons.
• Isotopes have similar chemical properties.

1H 2H 3H

131 I 125 I 123 I


53 53 53
31
isomer
• Isomers are nuclides having the same number
of protons and neutrons , but different energy
state.

• 99m
43Tc ,
99
43Tc .

32
 
99
42 Mo  Tc Tc   (140keV )
99 m
43
99
43
66 h 6h
• nuclide
• isotope
• isomer

34
Why are some atoms radioactive?

• Radiation is energy given off by some


atoms in the form of particles or rays.

35
• An atom is radioactive (unstable) if
these forces among the particles that
make up the nucleus are unbalanced.

36
The first force
• Electric (or Coulomb) force is attractive
when the charges are opposite and repulsive
when the charges are alike.

• Opposite Charges Attract

• Similar Charges Repel

37
The second force

• strong interaction or strong nuclear force


• between any two nucleons
• This force, although much stronger than
the electric force when nucleons are close
together, falls rapidly to zero if the
nucleons are separated by more than 10-13
cm.
38
The third force
• Weak interaction is much weaker than the
electric or strong interaction.
• It has the ability to change neutrons into
protons, and vice versa (transmutations) .

39
The fourth force

• Gravity -- all the constituents of the atom

The strength is some 1040 times smaller than that of the


electric force. 40
• An atom is radioactive (unstable) if
these forces among the particles that
make up the nucleus are unbalanced.

41
stable nuclide

unstable nuclide (radionuclide)

radionuclide: it refers to the unstable nuclei


spontaneously emit radiation (such as alpha,
beta ray) to form another nuclei or nuclear
energy state by decay.

42
Radiation decay
The process by which an atomic nucleus of a
radionuclide spontaneously emits radiation and
simultaneously transforms into another nucleus

43
Radiation decay

• Alpha ( α ) decay
• Beta-minus ( β -)decay
• Beta-plus ( β +) decay
• Electron capture
• Gamma (γ) decay

44
Radiation decay
1. Alpha (α) decay
2. Beta-minus( β -) decay
3. Beta-plus ( β +)decay
4. Electron capture
5. Gamma (γ) decay
45
Alpha (α) decay
• Heavy nuclei tend to be unstable because
they contain large numbers of protons
that strongly repel each other.
• mass number > 56

46
Alpha(α) decay

• The alpha particle consists of :


two protons and two neutrons, being
identical to a 42He nucleus without the
orbiting electrons:
• A X → A-4Z-2Y + 4
Z 2He +Q(Decay energy)
47
• Alpha particles travel only microns
in soft tissue.

• present a serious radiation hazard


when they deposited within the body.

48
A portion of the 238U decay chain showing the alpha decay
of 222Rn to its polonium daughters.
49
Radiation decay
1. Alpha decay
2. Beta-minus decay
3. Beta-plus decay
4. Electron capture
5. Gamma decay
50
Beta-minus decay

• A nucleus that has too many neutrons for


stability cannot simply emit a neutron 51
Beta-minus decay. A neutron is transformed into
a proton in the nucleus with the emission of an
electron and an antineutrino.
52
Beta-minus decay
• The antineutrino is the antiparticle of an elusive entity
called the neutrino.

• A X → AZ+1Y + βˉ + υˉ + Q
Z

• 32 P = 32 S +β- +υ- + 1.71Mev


15 16

proton
electron

53
neutron antineutrino
Beta-minus decay (133Xe to 133Cs), leading to the
emission of gamma radiation. It is the 81-keV photon
that is imaged in gamma camera studies.
54
Radiation decay
1. Alpha decay
2. Beta-minus decay
3. Beta-plus decay
4. Electron capture
5. Gamma decay
55
Beta-plus decay
• a proton is transformed into a neutron
with the emission of a positron(e+ )and
a neutrino(υ)
• Proton →Neutron + Positron + Neutrino
• AZX → AZ-1Y + e+ + υ
positron

neutrino

56
Beta-plus decay. A proton is transformed into a neutron in
the nucleus with the emission of a positron and a neutrino.
The positron travels only a short distance in tissue before
annihilating with an electron to produce two 511-keV
photons. 57
Radiation decay
1. Alpha decay
2. Beta-minus decay
3. Beta-plus decay
4. Electron capture
5. Gamma decay
58
Electron capture
• It is an alternative to beta-plus decay, electron
capture, that accomplishes the same result.
• Proton + Orbiting electron → Neutron +
Neutrino

• A X
Z + e- → AZ-1Y + υ + Q

59
• Photons produced when electron moves
from a higher energy shell to a lower
energy shell are called characteristic (or
fluorescent) X rays.

• The energy of the characteristic X ray is


the difference in energy between the two
shells.

60
Emission of a characteristic X ray when an electron
drops from the L shell to fill a vacancy in the K shell.

61
• Auger electron

Auger process. an Auger electron may be ejected from the atom


(here, from the M shell) when an electron moves to a shell of
lower energy.
62
• The emission of characteristic X rays dominates in
high-Z materials.

• The expulsion of an electron is much more likely in


low-Z elements ( Auger electrons)
63
Internal conversion
• When a nucleus shifts from a high-energy
state to a low-energy state , the excess
energy is transmitted directly to electrons ,
it can send electrons out.

64
internal conversion
• After internal conversion occurs , vacancies are
left in the K or L layers of the atom .
• Characteristic X ray and Auger electrons will
also be generated.

65
Radiation decay
1. Alpha decay
2. Beta-minus decay
3. Beta-plus decay
4. Electron capture
5. Gamma decay
66
Gamma decay

• A nucleus in an excited condition will


eventually return to the ground state .

• The movement of nucleons to lower


energy orbits typically gives rise to the
emission of photons called gamma rays. 67
• Often, when a radionuclide decays, the decay
product is radioactive , too.
• go through many steps decay.
'decay chain.'

Am
ZX →A X+γ
Z
99m Tc → 9943Tc + γ
43

 
Mo  43Tc   (140 keV )
Tc 99
99 99 m
42 43 68
66 h 6h
Radiation decay
1. Alpha decay
2. Beta-minus decay
3. Beta-plus decay
4. Electron capture
5. Gamma decay
69
How long do radionuclides stay
radioactivity?

• It depends on the type of radioactive


materials.
• The rate of decay is one of the
characteristics of radionuclides.

70
Decay law
half-life
T1/2 : the half-life of the radionuclide.

a time period that the number of nuclei


decrease by one-half.

71
Decay law

• N=N0 exp-λt
• exp = 2.718
• λ = fraction of nuclei decaying per unit time
• units: 1/time.
• λ:decay constant
• Each has its unique decay constant.

72
Biological half-life, Tb

• Tb is the time an organism takes


to eliminate one half the amount
of a compound or chemical on a
strictly biological basis.

73
Effective half-life, Te

1 1 1
= +
Te T1/2 Tb

74
Radioactivity

• The size or weight of a quantity of


material does not indicate how much
radioactivity is present.

75
Radioactivity

• Radioactivity is measured in units of


becquerel (Bq).
• 1 Bq = 1 event of radiation emission per second.

76
Radioactivity
• One becquerel is an extremely small amount
of radioactivity.
• Commonly used
• kBq (kilobecquerel)103
• MBq (megabecquerel)106
• GBq (gigabecquerel)1012
77
unit of measuring radioactivity
curie (Ci) / mCi / Ci / nCi;

1 Ci = 3.7×1010 Bq

78
Interaction of radiation with matter

• Interaction of charged particles with matter


• Interaction of photons with matter

79
Interaction of charged particles
with matter
• Ionization
• Excitation
• Scattering
• Bremsstrahlung
• Absorption
• Cherenkov radiation

80
Interaction of charged particles
with matter

• Ionization
• Excitation
• Scattering
• Bremsstrahlung
• Absorption
• Cherenkov radiation

81
Ionization
• It refers to the process of forming free electrons and positive
ions by the electrostatic interaction between the charged
particles and the outer electrons of the material atoms.

82
Interaction of charged particles
with matter
• Ionization
• Excitation
• Scattering
• Bremsstrahlung
• Absorption
• Cherenkov radiation

83
Excitation
• When charged particles pass through the material, the energy
obtained by the nuclear electron is not enough to make it out
of the atom, but only from the inner layer to the outer layer.

• the atoms become excited states from the steady states.

84
Interaction of charged particles
with matter

• Ionization
• Excitation
• Scattering
• Bremsstrahlung
• Absorption
• Cherenkov radiation
85
Scattering

• After the collision between the charged particles (Beta ray) and
the nucleus of the material, the movement direction and the
energy of the particles are changed.

86
Interaction of charged particles
with matter

• Ionization
• Excitation
• Scattering
• Bremsstrahlung
• Absorption
• Cherenkov radiation
87
Bremsstrahlung
• Fast electrons pass through the material, under
the action of electric field in atomic nucleus, the
direction of motion is changed, and the speed is
reduced dramatically, a part or all of the electron
energy is converted into a continuous energy by
the X - ray emission.

88
Interaction of charged particles
with matter

• Ionization
• Excitation
• Scattering
• Bremsstrahlung
• Absorption
• Cherenkov radiation
89
Absorption

• In the process of ionization and


excitation of the atoms in the material by
the charged particles, the energy of the
rays is completely depleted, and the rays
are no longer in existence.

90
Interaction of charged particles
with matter

• Ionization
• Excitation
• Scattering
• Bremsstrahlung
• Absorption
• Cherenkov radiation
91
Cherenkov radiation
• When velocity of charged particles in the
medium is greater than the speed of light,
they will emit a faint with short
wavelength based radiation, called
Cherenkov radiation.

92
Interaction of charged particles
with matter
• Ionization
• Excitation
• Scattering
• Bremsstrahlung
• Absorption
• Cherenkov radiation

93
Interaction of photons with matter

1. Photoelectric effect
2. Compton effect
3. Pair production

94
Photoelectric effect
• A photon interacts with the atom, losing all its
energy in the process.
• An inner shell electron (usually a K shell electron)
is ejected from the atom, leaving a vacancy in the
inner shell.
• When the vacancy is filled by another electron,
photons (characteristic X rays) will be emitted.

95
Photoelectric effect of a photon by an atom, resulting in
the ejection of an inner-shell electron. When the electron
vacancy is filled, characteristic X rays and Auger electrons
will be produced. 96
Compton effect( Compton scattering)
• To "scatter" means to change direction.
• A photon interacts with an outer shell electron in an atom
of the material that the photon is traversing.

• The photon changes direction after meeting the electron,


the electron is knocked away from the atom, and the
photon loses whatever energy the electron acquires .

97
Compton effect of a photon from an outer-shell electron
through angle A. The electron is set into motion with an energy
equal to that which the scattered photon loses. 98
Pair production
• A photon interacts, not with the atomic electrons, but
with the electric field of the nucleus. In the process the
energy of the photon is converted into mass, an electron
and positron pair can be produced .

99
Pair production process in which a high-energy
photon in the neighborhood of the nucleus of an
atom is transformed into an electron and
positron pair. 100
Interaction of photons with matter

1. Photoelectric effect
2. Compton effect
3. Pair production

101
Radiation Protection

102
Alpha(α)

paper thin aluminum


sheet Lead or
Beta concrete

Gamma

103
Common radiation
protection equipments

104
Basis of radiation dosimetry

• the amount of exposure


• absorbed dose
• dose equivalent

105
The amount of exposure

• Irradiation (X): it can measure the ionization


effect of gamma rays on the air, which can
reflect the intensity of the radiation field of the
gamma ray. It is a physical quantity to
measure the intensity of the radiation field.

106
Unit of exposure

• The international system of units :C · kg -1

• The old private units : R( Roentgen), mR μR。


1 R = 2.58×10 -4 C · kg -1
1 C · kg -1 = 3.877×10 3 R

107
Absorbed dose

• Absorbed dose(D):It is used to mean


that the average energy of the unit mass is
absorbed by the ionizing radiation.

108
The unit of absorbed dose
• The international system of units : Gy
• 1 Gy means that the radiation energy absorbed
by the 1 kg substance is 1 J.
• 1 Gy = 1 J · kg -1
• The old private unit : rad
1 Gy = 100 rad

109
Dose equivalent
• dose equivalent( H) :
– The biological effects of various kinds of rays on the tissue
are not only related to the absorbed dose, but also to the
types of the rays.
– An amount of ionizing radiation that is set on the basis of the
absorbed dose to account for the different biological effects,
It is an ionizing radiation that directly reflects
the biological effects of various rays or
particles being absorbed.

–H = D·Q ·N
D for the absorbed dose, Q for the quality factor, N for the
distribution factor, is the product of any other correction factor.
110
The unit of dose equivalent

• The international system of units : Sv


1 Sv = 1 J · kg -1
• The old private units : rem(雷姆)
1 Sv = 100 rem

• Dose equivalent rate(H):Dose equivalent


per unit time.
• H=dH/dt
• The international system of units :Sv · s -1 ,
• The old private units :rem · s-1 .

111
The commonly used radiation quantities and
units in comparison table

辐射量 国际制单位 专用单位


名称(符号) 名称(符号) 单位换算关系
通名(符号) 专名(符号)

放射性活度 1/秒 贝可 居里
(A) (S-1) (Bq) (Ci) 1mCi =37MBq

照射量(X) 库仑/千克 伦琴
([Link]-1) (R) [Link]-1=3.88 x103R

吸收剂量 焦耳/千克 戈瑞 拉德
(D) ([Link]-1) (Gy) (rad) 1Gy =100rad

剂量当量 焦耳/千克 西沃特 雷姆


(H) ([Link]-1) (Sv) (rem) 1Sv =100rem

112
Types of radioactive irradiation

1. Internal irradiation

2. External irradiation

3. Brachytherapy

113
Natural background exposure

• cosmic radiation
• earth radiation

114
Natural background exposure

115
Radiation effects

• International Commission of Radiation


Protection (ICRP) :
1. determinate effects;
2. stochastic effects

116
Determinate effects

• The severity of the effect varies with the dose


and the effects are not seen below a certain
threshold level of radiation.

117
Cataracts:

• A minimum dose of 200 rem (2 Sv) is required for


the development of cataracts.

• The threshold for developing a vision impairing


cataract under conditions of prolonged,
fractionated exposure is felt to be 800 rem (8 Sv).

118
Stochastic Effects

• These effects have no threshold and the severity of


the effect does not vary with the dose.

• The probability of occurrence, however, increases


as the dose increases.

119
Stochastic Effects

• Cancer is a stochastic effect, particularly leukemia


which has a latent period of 2 to 10 years post
exposure.
– The risk for leukemia is significantly increased
above acute doses of 40 rads (0.4 Gy).

• Genetic effects, Mutagenesis

120
Principles of radiation protection

1. Justification
2. Optimization

3. Individual dose and risk limitation

121
Justification:
No practice involving exposures to radiation
should be adopted unless it produces enough
benefit to the exposed individuals or to society
to offset the radiation detriment it causes.

122
Optimization:
• Exposures to radiation should be as low as
reasonably achievable.

Individual dose and risk limitation:


• No individual should receive radiation doses
higher than the maximum allowable limits.

123
Radiation Workers

• Whole Body: accumulative equivalent dose less


than 100mSv in continuous 5 years,
• and less than 50mSv among any year.

– Lens: 150mSv
– Skin: 500mSv
– Other organs: 500mSv

124
Non-radiation worker

• Accumulative yearly equivalent dose less than


1mSv,
• or yearly average dose less than 1mSv in
continuous 5 years
• (not including patients who received diagnostic
or therapeutic radiopharmaceuticals) .

125
External radiation protection
measures

time
1. Time
2. Distance

3. Shielding

distance shielding

126
Time

• The amount of radiation exposure increases or


decreases with the time people spend near the
source of radiation.
• Gamma and x-rays are the primary concern for
external exposure.

127
Distance

• As a rule, if you double the distance, you


reduce the exposure by a factor of four.
• Halving the distance, increases the exposure by
a factor of four.

128
129
Shielding

• The greater the shielding around a radiation


source, the smaller the exposure.
• The amount of shielding required to protect
against different kinds of radiation depends on
how much energy they have.

130
Shielding

131
Radiation Protection

132
Imaging Types

133
the types and characteristics
of the imaging
(1)static imaging and dynamic imaging
the state of image acquisition
(2) regional imaging and whole body imaging
the scope of image acquisition

134
the types and characteristics
of the imaging
(3) planar imaging and tomography
the projection method of image acquisition
(4) early and delayed imaging
the time of image acquisition
(5) positive and negative imaging
the uptake of the lesion tissue to the imaging agent

135
the types and characteristics
of the imaging
(6) resting and loading imaging
the state of the body when the imaging agent is ingested
(7)single photon imaging and positron imaging
the type of the imaging agent

136
Static imaging and dynamic imaging

1. static imaging: The distribution of the


imaging agent in the organ or the pathological
changes is stable when the imaging is carried out.

Static imaging
137
Static imaging and dynamic imaging

2. dynamic imaging: After the


imaging agent is introduced into the
body, the continuous image of the
dynamic collecting organ is quickly
carried out with preset speed.

dynamic imaging

138
• 3. whole body imaging
– Use SPECT or check the bed uniform
movement, from head to foot collect the
radioactive distribution of the body parts, and
finally compose a complete whole body image;
– Commonly used in the whole body bone scan,
bone marrow imaging, to detect tumor or
inflammatory lesions, etc.

139
4. regional imaging:
– only display an image of a part of the body
or an organ.
– This method has a large amount of
information, high resolution, the most
commonly used clinical.

140
Regional imaging Whole body imaging

141
Regional imaging Whole bodimaging

142
5. planar imaging
– The detector of imaging
device is placed in a
certain position of the
body surface to collect the
radioactive information of
a certain organ.

143
6. tomographic imaging
– Use a rotatable or annular detector on body
surface to continuously collect multi position
planar image data, And then form a variety of
tomographic images by computer reconstruction
– Such as: cross section, coronal and sagittal
images, etc..

144
Planar imaging

Tomographic imaging
145
7. early imaging : Imaging be occurred within
2 h after injection of the imaging agent.
• mainly reflects the organ perfusion and early
functional status.

8. delayed imaging: Imaging be occurred


2 hours and above after injection of the
imaging agent.

146
early imaging and delay imaging

30min 3h

147
9. positive imaging (hot spot imaging)
•Imaging agent is mainly avid in the lesion ,
and generally not or rarely by normal
[Link] radioactivity of lesion is higher than
that of the normal tissue, show "hot spot"
changes.

148
10. negative imaging (cold zone imaging)
•The imaging agent is accumulated mainly in the
normal tissue , while the pathological tissue is not
accumulated, the performance of the radioactive
distribution is sparse or defect Static imaging.

149
positive imaging negative imaging
11. rest imaging
– It refers to the subject in a quiet state,
not by physiological stimulation or
drug interference, when the imaging
agent is introduced into the human
body or the image is collected

151
12. stress imaging (interventional imaging)
– It refers to the use of drugs or physiological stimulation
and other methods to increase the function of an organ or
load, through the observation of organs or tissues to
stimulate the response ability, can judge the organ or
tissue perfusion reserve function.
– And increase the difference of radioactivity distribution
between normal tissue and diseased tissue, it is beneficial
to find the pathological changes which are not easily
observed in resting state, so as to improve the sensitivity
of imaging diagnosis.
152
rest imaging and stress imaging
Stress Rest Stress Rest

Myocardial
Perfusion
Imaging

153
[Link] photon imaging:It refers to the use of a
single photon detection equipment (SPECT) for
single photon imaging radionuclide emission in
imaging agent
[Link] imaging:It refers to use imaging
instrument for detecting positron to scan
positron emission from radionuclide
(coincidence SPECT and PET)

154
single photon imaging and
positron imaging

Single photon imaging Positron imaging

155
156
 Nuclear Medicine (NM) is a medical
specialty for diagnostic and
therapeutic use of unsealed
radionuclides.

using small amounts of radioisotopes as


tracers to diagnose disease, or larger
amounts for therapy.
In vivo methods
There are two types of in vivo In vitro test
techniques: imaging and non- make use of samples
imaging techniques. taken from the patient
A patient is usually given a such as blood
radioactive material or
radiopharmaceutical
intravenously. It accumulates
in the target pathological area
and can thus be detected by
external equipment. Radionuclide therapy
such as the treatment of
hyperthyroidism, thyroid cancer, and
pain relief from certain bone
cancers.
 Endocrinology is a specialty of medicine

concerned with the endocrine glands in


the human body and the diagnosis and
treatment of endocrine system disorders.
The endocrine glands of the body include the pituitary,
thyroid, parathyroid, pancreas, ovaries and testes,
adrenals, pineal and thymus gland. Hormones are the
products of the endocrine glands and are transported in
the blood to maintain the body's functional balance.
 Disorders of the endocrine system
 Diabetes mellitus

 Cushing’s syndrome

 Addison’s syndrome

 Hyperthyroidism

 Hypothyroidism

 Osteoporosis

 Cancer

…

Disorders of the endocrine system involve either


underproduction or overproduction of the body's hormones.
What is Nuclear Endocrinology (NE)?

Nuclear Medicine NE Endocrinology

A branch of NM,
Using radionuclide to diagnose or treat endocrine disorders.
NE was the first clinical use of radionuclides, about six decades ago.
Dr Joseph G. Hamilton.
Who was the first to give
radioiodines to humans to
study iodine physiology.

Measurement of thyroid uptake


after oral ingestion of 131I sodium
iodide. Made around 1940.
 The first major achievement of nuclear medicine was in
endocrinology.
 in 1942, A. Hertz and A. Roberts published the results

of the first application of radioactive iodine in therapy


of Graves’ disease;
 in 1946, a dose of iodine-131 halted the growth of
thyroid cancer and was found to be a useful tool in
diagnosing and treating thyroid diseases.
 This new method of organ imaging and disease
treatment was invaluable and marked the beginning of a
new era in medical history.
Rosalyn Sussman Yalow, in 1977 was awarded the Nobel Prize in
Physiology or Medicine for the development of the radioimmunoassay (RIA),
a method of quantifying minute amounts of biological substances in the
body using radioactive-labeled material. After that, many endocrine
problems were resolved by RIA.
SPECT
Hormone
Determination PET
Endocrinology
Function Radiolabelled
Test peptides
Radionuclide
Treatment

From those days to the present, nuclear medicine has a definitive role in the diagnosis
of a great variety of clinical situations. Radioiodine I131 still remains a very effective
treatment for Graves disease and differentiated thyroid cancer. New techniques, like
positron emission tomography (PET) and newer radiolabeled peptides, will offer a
molecular approach to the today clinical Nuclear Endocrinology .
 This chapter describes nuclear medicine techniques
available for endocrine organs.
1. Thyroid imaging and Radioactive iodide uptake test
(RAIU) are of great importance and are introduced
with emphasis.
2. Parathyroid imaging has a active role in the
management of patients with hyperparathyroidism
by diagnosing and localizing hyperfunctional
parathyroid glands.
3. Briefly introduce methods for imaging the adrenal
cortex and medulla.
Normal thyroid gland is located in the front of the neck (in the middle
of the lower neck, below the larynx and just above collarbones).

The thyroid gland originated in the base of the pharynx and


then migrates caudally to the level of the cricoid cartilage.
The thyroid lies just below the surface of the skin
and therefore is readily accessible for
examination, both visually and by palpation.
pyramidal lobe

The normal thyroid is a bilobed organ with butterfly-like shape on its projection.
Both lobes can be connected by the isthmus. Normally weighing less than 30 g.
In some cases, there may be pyramidal lobe and functioning remnants in the
place of ductus thyreoglossus.
Follicles surrounded
by cuboidal epithelium
follicular cells
are basal functioning
unit

Colloid inside the


cavity containing TG
and thyroid hormones

parafollicular cells
produce calcitonin
 Thyroid function
 Concentrate Iodide &Produce Thyroid hormone (TH)

 Thyroid epithelial cell concentrate iodide actively from


plasm. Using iodide as substrate, Thyroid epithelial cell
produce TH.
 T4 (thyroxin) and T3 ( triiodothyronine )

 General stimulating effect on metabolism, growth,

development, reproduction,etc.
 Produce thyroglobulin (TG)

 Thyroglobulin is a glycoprotein and contains tyrosyl

residues. It serves as a matrix in which thyroid hormone


is formed and also is the storage form of thyroid hormone.
 3 basic steps involved in TH synthesis
(also steps of iodide metabolism in thyroid)

 Step 1: Iodide trapping & concentration


 Step 2 : Oxidation & Organification

 Step 3: Proteolysis & release


Metabolic Processes of iodide in thyroid

Oxcidation & Orgnification The


Trapping Iodide in plasma is iodide is further oxidised by thyroid peroxidase and
highly concentrated in the thyroid cells bound to tyrosine on the surface of TG to
synthesize thyroid hormone,T3 and T4

tyrosyl

- I
I- I TG

T3 TG
T3 TG T4
T4 T3
T4
Proteolysis & release If needed, Tg with TH on its surface be uptake
into thyroid follicular cell. Proteolysis of thyroglobulin produces the active hormones
T4 and T3, which are then secreted into the blood.
 Thyroid hormone levels are regulated
by a feedback inhibition mechanism
that operates along the
hypothalamic-pituitary-thyroid axis.
 The hypothalamus secretes TRH
which promotes pituitary secretion of
TSH.
 TSH, in turn, is necessary to
stimulate the thyroid to produce and
release thyroid hormones.
 The return of thyroid hormone
concentrations is sensed by
receptors on the pituitary and
hypothalamus, and further production
of the stimulating hormones
produced by these glands is inhibited.
 Hyperthyroidism  Nodule
 Hypothyroidism  Adenoma
 Thyroiditis  Carcinoma
 Goiter
NM Approaches to Thyroid Diseases
 Radioactive iodide uptake test

 Thyroid scintigraphy

 Radioiodide treatment
Most commonly used isotopes in thyroid

 131
I, Radioiodine-131

123I, Radioiodine-123

 99Tcm , Technetium-99m

Comparing to standard radiography, nuclear medicine images (scans or


scintigraphies) always require the administration of radioactive tracers.
These radiolabeled drugs, named radiopharmaceuticals, usually reflect the
blood flow, the capillary permeability or the specific tissue extraction.
 131 I
 delivers both beta and gamma radiation
 gamma energy is 364 keV

 half-life is 8 days

 used for
 Thyroid uptake test
 Thyroid imaging

 Therapy
 123 I
 pure gamma radiator
 energy of 159 keV

 half-life of 13 hours

 it has ideal properties for imaging but its


cost is high
 used for imaging only
 99 Tcm (99Tcm O4-)
 pure gamma emitter
 energy 140 keV

 half-life 6 hours

 it is not organified, after trapping it is


relatively quickly released back to the
blood
 Used for imaging only
 Radioactive iodide uptake test (RAIU)
 The ability of thyroid iodine uptake reflects the
metabolism status of thyroid gland
 High radioiodine uptake reflects hyperactive
metabolism
 Low uptake reflects hypoactive metabolism
 Radioactive iodide uptake (RAIU) is the
percentage of administered radioiodine
incorporated by the thyroid gland.
 Patient Preparation
 Avoidance of Interfering Materials
 Medications such as thyroid hormones and

antithyroid agents which affect the pituitary-


thyroid axis.
 Iodine-containing food (e.g. kelp) and

medications (e.g. iodinated contrast,


amiodarone).
 Recent administration of radionuclides
 Be in fasting state in the exam morning
 Large meals can slow absorption of ingested
radioiodine and may interfere with early uptake
measurements.
 Radiopharmaceuticals
 131I

 Activity : 5μCi
 Orally Administration
The neck phantom is a solid
cylinder composed of acrylic and
contains a cutout for a 30 milliliter
bottle containing iodine compounds.
The body of the phantom simulates
the overall size, shape, density, and
attenuation of the human
neck.( simulate portions of adipose
and muscle tissue ).

Neck Phantom (Standard Activity)


Instrument of thyroid uptake test.
Detect and record gamma rays as counts.
 Measurement & Calculation

 Return visit at 2, 6, 24hrs after


 To obtain counts of (detect gamma
rays from )
 Background

 Neck

 Standard activity (Neck


Phantom)
Neck Counts (cpm) – Background Counts (cpm)
RAIU = ×100%
Standard Counts(cpm) – Background Counts (cpm)

 cpm: counts per minute


 RAIU reference range SNM Guideline
 2hr: 10~25% 4 hr: 6 ~18%
 4hr: 15~30%
 24hr: 25~50% 24 hr : 10~35%

The normal range should be established locally. This is normally


determined by the dietary iodine intake, types of equipment, standard
applications and uptake phantoms.

The interpretation of uptake should be made in conjunction with the


patient’s history and drug medication intake.
Normal: Uptake increases with time and the peak at about 24hrs
GD: Uptake higher than normal and the peaktime less than 24h

A low uptake value is not a primary diagnostic criterion for hypothyroidism.


 Increased I-131 Uptake
Diseases
 Graves’ Disease
 Toxic multinodular goitre
 Solitary hyperfunctioning nodule
Other situations
 iodine deficient
 Rebound after withdraw of ATD/TH
 Decreased I-131 Uptake
Diseases
 Hypothyroidism: Primary or Secondary, Surgical/Radioiodine
Ablation of Thyroid
 Thyroiditis: Acute, Subacute and Chronic Lymphocytic
 Renal failure, congestive heart failure: increased iodide retention
Other situations
 Iodine overload(medicine, food)
 Thyroid hormone
 Anti thyroid drugs
 Adrenal cortex hormone
 Clinical indications
Thyroid uptake measurements can be made for the following
reasons
 To determine the functional status of the thyroid gland

 To calculate specific doses of


131I for the treatment of

hyperthyroidism
 To differentiate subacute or painless thyroiditis and

factitious hyperthyroidism from Graves’ disease


T3T4 T3T4 RAIU
Normal
limitation
RAIU

“separation” “parallel”

Subacute thyroiditis Graves disease


Toxic phase
 Clinical contraindications
 Pregnancy

 Nursing status


131I freely pass through the placenta, foetus thyroid is
able to accumulate iodine since approximately 12th
week.

131I also pass to the breast milk and breast-feeding

must be stopped
 Perchlorate Discharge Test
This test is used to identify congenital or acquired
organification defects which most commonly involves the
enzyme iodide peroxidase.
 Principle
 Perchlorate (ClO4-)
 inhibit active iodide transport
 cause the release of the intrathyroidal iodide not bound to

thyroid protein.
 In normal subjects, radioiodine when taken up by the thyroid is
immediately organified and bound to thyroglobulin. However, in
patients with defects in peroxidase activity (usually hypothyoid),
trapped radioiodine is rapidly discharged when sodium perchlorate is
administered.

 Positive result indicate the presence of an defect of


iodide organification.
KClO4-
KClO4 -
-
I I- TPO
TPO
I- I -

I- I- I- I- I
I-
I- T3 Tyr
T3 TG
T4 TG
T4
Organification defect:
non-organified iodide
washes out ,
radioactive counts
decreased.
 Procedure

1st 2h RAIU KClO4 600mg,po 2nd 2h RAIU

 Calculation
1st 2h RAIU—2nd 2h RAIU
Discharge Rate= ×100%
1st 2h RAIU
 Interpretation
Discharge Rate <10%, normal
Discharge Rate >10%, disorders of iodide
organification
 Congenital hypothyroidism
 Hashimoto thyroiditis

 Pendred syndrome

 Graves’ disease
 RAIU Test
 Clinical indications

 To determine the functional status of the thyroid gland


 To calculate specific doses for the treatment of
hyperthyroidism
 To Differentiate subacute or painless thyroiditis and
factitious hyperthyroidism from Graves’ disease
 Perchlorate Discharge Test
 Indicate the presence of an defect of iodide organification
 Thyroid Scintigraphy
 A variety of imaging modalities can be used to
image thyroid including thyroid scintigraphy,
ultrasound, CT, and MRI.

 Practically speaking, scintigraphy and ultrasound


have been most widely used.

 Thyroid scintigraphy distinctively shows the


functional state of thyroid gland.
 Thyroid scintigraphy is a procedure producing images of the
thyroid obtained after administration of radioactive tracer.
 Thyroid scintigraphy is based on iodide physiology involving the
following: iodine ingestion, trapping and concentration in the
thyroid, oxidation and organification to produce iodotyrosines,
and a coupling process to form thyroid hormones.
 In thyroid imaging, the radioiodine is readily taken up by the
thyroid gland, where it is trapped and concentrated from the
plasma, and then undergoes the organification process.
 Similarly, the pertechnetate ion is also trapped and
concentrated by the thyroid gland but it does not
undergo organification.
 The presence of high concentrations of these
radiotracers in the thyroid gland provides excellent
visualization of the gland by the gamma camera.
 Radioactive imaging agent
 Thyroid Uptake / γ-ray
 Most common: 123I, 131I, 99TcmO -
4
 Others: 18F-FDG, 99Tcm-MIBI
Advantages Disadvantages
Iodine-123 Short half life (13.3h) Higher cost
Pure gamma emiter Less readily available
Iodine-131 readily available Long half life
Long stock time beta particle emission
Tc-99m Less expensive Trapped, but not organified
pretechnetate More readily available Activity in esophagus or
More rapid examination vascular structures can be
misleading
Low radiation exposure
 Instrument
 γ-camera, SPECT,PET
 Collimator : Pinhole
 Thyroid scintigraphy may be required for any of the
following purposes:
 To determine the size of the thyroid gland;
 For localization of thyroid nodules;
 To determine the activity of thyroid nodules;
 To determine functional status of the thyroid gland;
 To evaluate presence of ectopic thyroid tissues, thyroglossal
duct cysts and substernal masses.
 Pregnancy and nursing
 Radiopharmaceuticals are contraindicated in
pregnant women.
 Enquiries should be made about the menstrual history of
female patients in the reproductive age group.
 Discontinuation of breast feeding for nursing
mothers
 Both 99mTc and all Iodine isotopes freely pass through the
placenta, foetus thyroid is able to accumulate iodine since
approximately 12th week. That is why 131I is contra-indicated
during pregnancy and others radionuclides should be used very
carefully.
 All these radionuclides also pass to the breast milk and breast-
feeding must be discontinued for 12 to 24 hours if we used
99mTc, for 2-3 days using 123I and must be stopped if we use

more than 70 kBq of 131I


 Patient position
 Patients should be positioned under the gamma
camera supine with the neck extended at a standard
distance from the collimator.
 Radioactive markers should be used to identify

 anatomical landmarks (e.g. sternal notch, thyroid


cartilage)
 the location of palpable nodules.
 Timing of imaging:
 For 123I: Imaging can be done 3–4 hours after oral
administration.
 For 131I: Images are obtained 24 hours post-

administration.
 For 99mTc-pertechnetate: Images are obtained 15–30
min after intravenous administration.
 The following should be assessed as
appropriate:
 Uniformity and intensity of the image of the thyroid
 The presence, absence, size, and location of areas of
increased or decreased uptake
 Functionality of nodules.
 Presence or absence of thyroid tissue.
 Presence of ectopic thyroid tissue.
 Presence of retrosternal extension.
 Normal thyroid scintigraphy:
 The typical “butterfly” shape, Pyramidal lobe visualized in some of patients
 Proper position : in the anterior neck area, above the sternal notch, in the region of the thyroid
cartilage.
 The normal dimensions: about 2×4cm
 The regular contour, without any interruption or mismatches.
 homogeneous radioactivity distribution: with intense colour in the middle of each lobe related to the
thickness of the thyroid tissue; the margins will have a less intense color, due to the decreasing quantity
of the thyroid tissue. The absence of nodules with different metabolic activities.
 Physiologically the right lobe may be larger than the left one.
Normal

The image below is a normal 99m technetium image of the thyroid gland. You can
see that technetium is not only localized in the thyroid gland but in the salivary
glands and other mucous secreting glands as well.

99TcmO -
4
 Trapping only
 Salivary uptake
 pathological findings
 Ectopic location
 Enlargement / Shrink
 Abnormal shape
 Diffuse/ Focal increasing or decreasing activity
 Intensely increased uptake in the gland denotes a diffusely
hyperplastic gland (e.g. Graves’ disease)
 Uptake in only one portion or one lobe is commonly seen post-
surgery or in hyperfunctioning autonomous adenomas
 Diffusely decreased tracer uptake or non-visualization may be
seen in cases with
 concomitant anti-thyroid medication
 an increased iodine pool
 under thyroid suppression secondary to thyroid replacement therapy
 subacute thyroiditis
1. Localization of Ectopic Thyroid Gland
2. Determination of Nodule Function
3. Differentiate Diagnosis of benign from
malignant
4. Differentiate Diagnosis of neck mass
5. Detection of thyroid cancer metastasis
6. Evaluation of thyroid weight
1. Localization of Ectopic Thyroid Gland
2. Determination of Nodule Function
3. Differentiate Diagnosis of benign from
malignant
4. Differentiate Diagnosis of neck mass
5. Detection of thyroid cancer metastasis
6. Evaluation of thyroid weight
An aberrant or ectopic thyroid gland may occur anywhere along the path of initial
descent of the thyroid,
If the thyroglossal duct does not atrophy, then the remnant can manifest clinically
as a thyroglossal duct cyst.
 Lingual thyroid: Absence
of tracer uptake in the
cervical area with the focal
radiotracer uptake at the
base of the tongue is the
typical pattern.

131I is preferred for its

specificity
 Lingual thyroid: The patient presented
for evaluation of a midline neck mass.
The 99TcmO-4 exam demonstrated the
abnormality to be due to a lingual
thyroid. No normal thyroid tissue can
be seen in the thyroid bed.
 One of differential diagnosis of a mediastenal mass.

Substernal Thyroid due to abnormal development of thyroid


I-131 is the first choice

Substernal thyroid due to the downward extension of an enlarged thyroid gland


1. Localization of Ectopic Thyroid Gland
2. Determination of Nodule Function
3. Differentiate Diagnosis of benign from
malignant
4. Differentiate Diagnosis of neck mass
5. Detection of thyroid cancer metastasis
6. Evaluation of thyroid weight
 A thyroid nodule
is a a lump, mass
or abnormal
growth of tissue
within the thyroid
gland.

 To correlate thyroid palpation with scintigraphic findings to


determine the degree of function in a clinically-defined nodule
 cold nodule demonstrates decreased
(absent) tracer uptake compared to
the surrounding normal thyroid tissue.
 hot nodule has greater more activity
than the normal surrounding thyroid
tissue

 warm nodule has activity equal to the


adjacent thyroid gland.
Nodule Radio- Disorders Malignancy
activity
Hot high Auto-functional adenoma, <5%
Congenital one lobe
Warm similar Adenoma, Nodular Goiter,
Thyroiditis
Cold low Cyst, Cancer, Hashimoto, 10%~25%
Hemorrhage / Calcified biopsy is
essential
1. Localization of Ectopic Thyroid Gland
2. Determination of Nodule Function
3. Differentiate Diagnosis of benign from
malignant
4. Differentiate Diagnosis of neck mass
5. Detection of thyroid cancer metastasis
6. Evaluation of thyroid weight
Thyroid Nodule

Differentiate Diagnosis of benign from malignant in cold nodules

Method Radio-agent
Tumor Positive Imaging 201Tl、99TcmO --MIBI、
4
Nuclear 99TcmO -- DMSA
4
Imaging
Metabolism Imaging 18F-FDG

Dynamic Perfusion Imaging 99TcmO -


4

Other B-ultrasound
methods
FNAB (Fine Needle Aspiration Biopsy)
99Tcm-MIBI Tumor Positive Imaging
201Tl Tumor Positive Imaging
99Tcm (Ⅴ) -DMSA Tumor Positive Imaging
1. Localization of Ectopic Thyroid Gland
2. Determination of Nodule Function
3. Differentiate Diagnosis of benign from
malignant
4. Differentiate Diagnosis of neck mass
5. Detection of thyroid cancer metastasis
6. Evaluation of thyroid weight
 neck mass
 Thyroid tissue?
 Functional ?
1. Localization of Ectopic Thyroid Gland
2. Determination of Nodule Function
3. Differentiate Diagnosis of benign from malignant
4. Differentiate Diagnosis of neck mass
5. Detection of differentiated thyroid cancer (DTC)
metastasis
6. Evaluation of thyroid weight
 Principle
 The process of uptake and organification consists in 131I
trapping in the thyroid gland and in all thyroid cells spread
in the body from a differentiated thyroid carcinoma (DTC).
 Radiopharmaceuticals: 131I
 Tumor positive : 18F-FDG, 99Tcm-MIBI, 201Tl
 Technique, 131I whole body scan :
 Patient preparation:
 Fasting for at least 6 h
 Thyroid hormone withdrawal /Thyrogen (recombinant TSH)
administration
 Avoid or limit the influence of the blocking drugs
 Attention to breastfeeding patient or potential fetal exposure

131I

 Administrated P.O. in case of the capsules or in liquid form


 Activities
 Diagnostic :2~3mCi,24~72h
 Therapeutic :100~200mCi,2~10days
 Clinical applications :
 Evaluation of remnant thyroid tissue post surgery in
DTC
 Decision about the extent of metastatic DTC

 Correct staging of DTC

 Assessment of the response to therapy in DTC


 Image Description :
 Physiologic uptake

 central facial area (nose, mouth)

 salivary glands (parotids,

submandibular glands)
 Stomach

 Bowel

 Urinary bladder

 There is a radioactive background

of the entire body


 Pathologic uptake:
 Thyroid remnant tissue in the neck
area
 Metastasis in the Lymph nodes, lungs,
brain,bones
 Any other site that express
radioiodine uptake, except the
physiologic ones
131I whole body scan:
remnant of thyroid after
surgery

One years later: lymph node metastases of thyroid cancer


Pulmonary metastases of thyroid cancer
Remnant of thyroid
Pulmonary metastases of thyroid cancer
Bone (Sternal & Tibial ) metastases of thyroid cancer
Radioiodine(-) 18F-FDG(+)
18F-FDG imaging: cine show
1. Localization of Ectopic Thyroid Gland
2. Determination of Nodule Function
3. Differentiate Diagnosis of benign from
malignant
4. Differentiate Diagnosis of neck mass
5. Detection of thyroid cancer metastasis
6. Evaluation of thyroid weight
 Planar Imaging
W=S×H×k (empirical formula Allen,1952)
 W, gland weight (g)
2
 S , size of area (cm )

 H, average lobe height (cm)

 K, 0.23~0.32 ( correction constant )


 Radiopharmaceuticals
 Most common: 99TcmO4- , 123I, 131I,
 Tumor positive: 18F-FDG, 99Tcm-MIBI, 201Tl

 Clinical Application of thyroid scintigraphy


1. Localization of Ectopic Thyroid Gland
2. Determination of Nodule Function
3. Differentiate Diagnosis of benign from malignant
4. Differentiate Diagnosis of neck mass
5. Detection of thyroid cancer metastasis
6. Evaluation of thyroid weight
 Parathyroid glands are pea-sized bodies located posterior to the thyroid
related to the upper and lower poles
 usually 4 glands (2 to 6 )
 it should not be larger than 7 mm, and their individual weight ranges
from 20 to 45mg
 ectopic localization in the area of neck (posterior to the esophagus) and
up mediastinum
 The parathyroid glands produce PTH, which is a key molecule
important for maintaining calcium, phosphate and vitamin D
homeostasis, and ultimately bone health.
 Low level of blood calcium stimulates production and secretion
of PTH, it mobilizes bone calcium and increases calcium
absorption in the bowel and kidneys.
 PTH preserves the calcium, phosphate and vitamin D
homeostasis through several main actions:
(a) stimulating renal tubular calcium reabsorption
(b) stimulating urinary phosphate excretion through the
inhibition of the sodium phosphate cotransporter NPT2a
(c) stimulating the activity of the 1α-hydroxylases and the
synthesis of calcitriol
(d) increasing calcium absorption from the gastrointestinal
tract via the stimulation of calcitriol production
(e) stimulating osteoclastic and osteoblastic activity in the bone
(bone remodelling) that results in the release of calcium and
phosphate from bone
 Hyperparathyroidism exists in three different
forms: primary, secondary and tertiary
 Primary hyperparathyroidism is characterized by
increased synthesis and release of parathyroid hormone, which produces
an elevated serum calcium level and a decline in serum inorganic
phosphates.
 Causes
 Hyper functioning adenomas (80%–85%)
 Parathyroid hyperplasia (12%–15%)

 Parathyroid carcinoma (1%–3% )


 Secondary hyperparathyroidism results from any
medical condition that tends to produce hypocalcaemia, resulting in
stimulation of parathyroid glands
 Chronic hypocalcemic condition that can be caused by
 renal failure
 Gastrointestinal malabsorption
 dietary rickets
 and ingestion of drugs, like phenytoin, phenobarbital and laxative,
which generate a decreased intestinal absorption of calcium.
 Secondary hyperparathyroidism is a frequent and serious
complication in haemodialysis patients.
 Tertiary hyperparathyroidism is a condition where
parathyroid hyperplasia, secondary to chronic
hypocalcaemia, becomes autonomous with
development of hypercalcaemia.
 Treatment
 surgical removal of abnormal parathyroid glands is
the most effective treatment
 the success of surgery depends on accurate

preoperative parathyroid lesion localization


Parathyroid Imaging

 There are a variety of anatomical and functional methods for


localizing abnormal parathyroid tissue
 Anatomic imaging
 B –mode ultrasound Imaging
 Computed Tomography
 Magnetic Resonance Imaging
 Functional imaging
 Nuclear Medicine: parathyroid scintigraphy
 B –US
 Advantage: High resolution
 Disadventage:

 extremely operator dependent


 affected by thyroid enlargement or nodular glands

 difficulty in identifying sites of disease

 when there has been previous surgery


 if there is an ectopic gland in the mediastinum.

 CT and MRI generally have been disappointing


 parathyroid scintigraphy
 Imaging hyperfunctional gland
 Specific & Sensitive

 localization (of adenomas or hyperplasia) to reduce

the time of operation


 Imaging Methodology

 Subtraction imaging refer to protocols using 2 different


radiopharmaceuticals for imaging acquisition

 Dual-phase imaging refers to utilizing single radiopharmaceutical


and acquiring early and delayed images
 Normal gland is invisible.
 Hyperfunctional gland usually visible
as one focus or multiple foci of
increased activity
Principle
 This method requires the visualization the thyroid gland and
then subtracting this image from an image of the thyroid and
parathyroid gland(s).
 Radiopharmaceuticals

201Tl( Thallous )
99Tcm-MIBI 99TcmO- 131I
4
Thyroid + + + +
Parathyroid + + - -

201Tl ---99TcmO-
4

99Tcm-MIBI ---99TcmO-
4
 Principle

99mTc-MIBI uptake in thyroid tissue was cleared

more quickly than that in parathyroid tissue.


 An image of the the neck is obtained within a few
minutes of its administration and then a delayed
image obtained 2 hours later.
 The method is simple to perform and involves only

one administration of tracer


 Early imaging
 15 to 30 min. after injection
 radioactivity both in thyroid and parathyroid

 Delayed images
 2 hrs later
 Thyroid washout faster

 radioactivity remains only in parathyroid


 The two sets of planar images (early and delayed) are inspected
visually.

 Focal areas of increased uptake, which show either a relative


progressive increase over time or a fixed uptake which persisted
on delayed imaging, must be considered pathological
hyperfunctioning parathyroid glands.
Ectopic parathyroid in mediastinum
Tomographic imaging using SPECT can give improved
localization of adenomas in terms of depth
 The minimally invasive
parathyroidectomy with
the aid of a radionuclide
probe
 The use of a probe to
localize the parathyroid
tissue requires the
injection of the
radiotracer approximately
2 hours before the surgery.
 Parathyroid Scintigraphy Methods (2) :
 Subtraction imaging
 Dual-phase imaging

 Clinical Application
 localizing of the hyperfunctioning parathyroid gland
(adenoma or hyperplasia) before surgery for shortening
operation time
 paired retroperitoneal
endocrine structures
localized superior and
medial to the kidneys.
 The adrenal glands consist of 2 embryologically,
morphologically, and functionally distinct units
the adrenal cortex, which is of mesodermal origin
and secrets steroid-derived hormones
 the medulla, which is of neural crestorigin and

secretes norepinephrine and epinephrine.


 Cortex
 Primary aldosteronism
 Cushing syndrome
 Adrenal hyperandrogenism
 Medulla
 Pheochromocytoma
 CT and MRI provide exquisite images of the adrenal glands and
offer the best initial imaging approach in the evaluation of
patients with suspected adrenal disease.

 However, they may fail to give the answer in some cases on


function.

 Adrenal gland scintigraphy uses radiopharmaceuticals with


specific imaging characteristics for the adrenal cortex and
adrenal medulla.
 These radiopharmaceuticals enter adrenal hormone synthetic
pathways and act as precursor or precursor-like compounds,
mimic native hormones, or demonstrate affinity for specific
endocrine tissue receptors and, in doing so, provide
information regarding target tissue endocrine function(s).

 Integrating information obtained from anatomic and


functional imaging has always been essential for
characterization of adrenal disease.
 Radiopharmaceutical

131I-6-iodocholesterol, 131I-6-IC

 Mechanism of accumulation
 Cholesterol is the principal metabolic precursor in the
synthesis of cortical steroids.

131I-6-IC ,cholesterol analog, transported by LDL (low-

density lipoproteins )
 after binding to adrenocortical cells the radiotracers is
internalized and esterified, but it is not further metabolized
 The uptake of the radiotracers by the adrenal glands
is related to
 Function status

 plasma ACTH level.

 plasma LDL level


Methods
 Non-suppressed exam

 Dexamethasone suppression exam


 Patient preparation
 Discontinuing of related medicines at least 2 weeks
 Thyroid blocking

 Lugol’s solution, 5~10 drops , tid


 From 3 days before imaging to the day imaging finished

 Laxative should be applied at night before imaging


 131
I-6-IC, 74~111MBq(2~3mCi), I.V.
 Imaging performed at 3,5,7,9 day after
131I-6-IC

administration
 Dexamethasone suppression exam
 One month after first imaging
 Dexamethasone 4mg qid, from 2 day before second
imaging to finish day
 Or 4 mg daily in divided doses for 7 days and
continued through the exam
 Normal adrenals are invisible or visible very
faintly
 Visualization of the normal adrenal glands can be
expected after 5 days
 The right adrenal gland appears round, more

intense, and slightly superior compared to the left,


which is oval
 Localization of radiotracers in the gallbladder may
be confused for right adrenal gland.
A. both adrenals are a. Both hyperplasia
visible b. One-sided adenoma (DSE needed)
c. Normal
B. one-sided a. Adenoma
accumulation b. Normal or compensatory hyperplaisa
(the opposite is cancer or absent)
C. bilateral non- a. Normal
visualization b. Cancer
c. Affected by medicine / markedly elevated
cholesterol levels
D. Ectopic Ectopic adrenal glands
accumulation
 Clinical Application
 Confirming diagnosis of adrenal cortex hyperfuction
 It distinguishes the different forms of Cushing’s syndrome
and of primary aldosteronism.
 Localization/Detection of postsurgical remenants
A 48-year-old female with ACTH-independent Cushing’s syndrome and a 3cm left
adrenal mass on CT scan which proved to be an adrenocortical adenoma when
resected.

live live

(A) Anterior (Ant) and (B) posterior (Post) abdominal 131I-6-IC scans without DS. The
black arrow indicates left-sided, intense adrenal uptake. Note that the right adrenal is
suppressed (not visualized) because of low ACTH; there is normal tracer uptake in the
liver ; faint colonic uptake is seen in the anterior view (A)
 Radiopharmaceuticals
 131 I-MIBG, 123I-MIBG
 Principle
 These radiotracers, like norepinephrine, accumulate
in sympathetic tissues and is stored by vesicles in
the synaptic adrenergic neuron.
 MIBG images the adrenal medulla and sympathetic

nervous tissue
 Patient preparation
 Withdraw related medicine
 Thyroid blocking

 using Lugol's solution or Super-saturated potassium


iodide (SSKI)

131I-MIBG 37~111MBq(1~3mCi)I.V.

 Imaging at 24h,48h,72h after administration


 Normal finding
 Normal adrenal gland

 non-visible or faint visualization


 Physiologic sites
 normal activity is seen in the large bowel, liver, spleen,
salivary gland, heart and urinary bladder
 decreases with time
A. Both adrenals are Both hyperplasia
visible, early intense

B. Adrenal intense Pheochromocytoma


accumulation in one
side

C. Accumulation a. Ectopic Pheochromocytoma


otherwhere b. Metastases of Pheochromocytoma
c. Neuroblastoma
 Clinical Application
 MIBG scintigraphy is particularly appropriate for
the study of extra-adrenal, multiple, and malignant
pheochromocytomas.
 MIBG scintigraphy is also useful in localizing

neuroblastoma, carcinoids and medullary thyroid


carcinomas.
A 73-year-old patient with left adrenal mass seen on MR,
and episodic hypertension by clinical history.
. A right adrenal mass on CT.

The patient is hypertensive


with elevated urinary
catecholamines

Intense tracer
accumulation in this
lesion which was
proven to be a
pheochromocytoma.
(A) Scintigraphy at initial 131I-
MIBG treatment showing
extensive bone metastases of
neuroblastoma.
(B) After treatment with three
131I-MIBG cycles (cumulative
dose: 400 mCi) and hyperbaric
oxygen a significant reduction in
tumor sites is observed.
Adrenal Cortex Imaging Adrenal Medulla Imaging

Radiopharm 131I-6-IC 123I-/131I-MIBG

localizing Pheochromocytoma,
neuroblastoma, carcinoids
Clinical study of adrenocortical and medullary thyroid
Application hyperfunction carcinomas
 Thanks
Chapter 6 Skeletal System

Huang Shanshan
2020-11-11
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Outline
• Anatomy and Physiology
• Radiopharmaceuticals
• Technique
• Normal Scan
• Clinical Applications
• Bone Marrow Imaging
• Bone Mineral Measurements
• Palliative Therapy of Painful Osseous
Metastases
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Anatomy and Physiology


• Bone is made of an inorganic mineral
phase of crystals bound to protein,
largely collagen.
The crystals consist of a composite
of calcium, phosphate, and hydroxyl ions,
called hydroxyapatite.
• The process of “bone turn-over”
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

skull、spine、
Axial portions
shoulder girdle

Skeleton
(Anatomically)
Appendicular upper extremities,
portions pelvis, and lower
extremities
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Radiopharmaceuticals
Technetium-labeled
diphosphonates (99mTc-MDP)

Fluorine-18 sodium fluoride


(18F-NaF)

Primary bone uptake mechanism:


Chemisorption
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

 99mTc-MDP

• phosphorus analog
• high target-to-nontarget ratio in 3 to
4 hours after injection
• rapid renal excretion
• impair renal function reduces the
quality of the bone scan
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Factors that may be responsible for


greater than usual activity Causes of Increased Activity on Bone Scan
Possible Mechanisms of Localized Generalized (Superscan)
Increased Activity on Bone Scans Primary bone tumor Primary hyperparathyroidism
Metastatic disease Secondary hyperparathyroidism
Increased osteoid formation Osteomyelitis Renal osteodystrophy
Increased blood flow Trauma Diffuse metastases
Increased mineralization of Stress or frank fractures Hematologic disorders
osteoid Physical abuse (nonaccidental trauma)
Interrupted sympathetic nerve Postsurgical osseous changes
supply Loose prosthesis
Degenerative changes
Osteoid osteoma
Paget disease, melorheostosis, fibrous dysplasia
Arthritis
Locally increased blood flow
Hyperemia
Decreased sympathetic control
Decreased overlying soft tissue
Soft-tissue activity
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

 18 F-NaF

• an analog for the hydroxyl ion in the


bone matrix
• 18F- OH-
• Initial uptake approaching 100%
• T1/2≈110min, high target-to-nontarget
ratio within 1 hour after injection
• drawback for 18F-NaF PET/CT :more
expensive and has a radiation dose
about seven times higher than that of
99m
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Technique
SPECT(99mTc-MDP)
a) routine planar scans
• normally injected intravenously with 10
to 20 mCi (370 to 740 MBq)
• imaged 2 to 4 hours after injection
• The site of injection should be
distant from any suspected osseous
pathology and should be recorded.
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

b)three-phase study
• radionuclide angiogram
• initial blood pool image
c) four-phase study
• additional images : performed 18 to 24
hours after injection
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Preparation
• Voiding before imaging
• Hydrate after injection and before
scanning
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

18 F-NaF PET/CT
• intravenously administered activity of
about 20 mCi (740 MBq)
• Whole-body scanning is done 1 hour
post injection
• CT scan is done without the use of
intravenous or gastrointestinal
contrast
• Limited body scanning
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Normal Scan

Fig1. Normal Adult Bone Scan [Link] Child Bone Scan


东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

 Anterior view:sternum, sternoclavicular


joints, acromioclavicular joints,
shoulders, iliac crests, hips,bladder
activity
 Posterior view:the thoracic spine is
well seen, as are the tips of the
scapulae;renal activity
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

• good visualization of the skull


:relatively increased accumulation of
activity in the region of the
nasopharynx
• focal maxillary or mandibular alveolar
ridge activity:adult、dental disease
• activity throughout the spine
• tendon insertion, chronic stress, and
osseous remodeling
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

 If urinary tract obstruction is suspected, kidney


views should be repeated after the patient has
ambulated to distinguish obstruction from position-
related collecting system activity.

[Link]. This
50-year-old woman with
cervical cancer had a bone
scan because of back pain
and suspected metastatic
disease. Anterior (left)
and posterior (right)
images show markedly
increased activity in both
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

 If there is
extravasation of the
radiopharmaceutical at
the site of injection,
the radiopharmaceutical
will be slowly resorbed,
lymphatic drainage may
also occur.

[Link] in
axillary lymph node
(arrow) after
extravasation of
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

 Localized areas of increased soft-


tissue or skeletal activity in an
extremity distal to the site of
injection (the glove phenomenon) may be
a result of inadvertent arterial
injection of the radionuclide
 Regional blood flow changes may also
be reflected in the scan
(atherosclerotic disease 、 gangrene,、
cellulitis or other inflammation)
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

 Recognition of the details of normal


imaging anatomy becomes even more
important
• Reviewing the images in three
orthogonal planes
• careful view of the sequential images
on a computer monitor display
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Clinical Applications
 Detection and follow-up of skeletal
metastases
 Differentiation between osteomyelitis
and cellulitis
 Determination of bone viability:
infarction or avascular necrosis
 Evaluation of fractures difficult to
assess on radiographs (stress fractures,
fractures of complex structures, and
possible fractures in children who are
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

 Evaluation of prosthetic joints for


infection or loosening
 Determination of biopsy site
 Evaluation of bone pain in patients
with normal or equivocal radiographs
 Evaluation of the significance of an
incidental skeletal finding on
radiographs
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Metastatic Disease
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

• The wide availability and high


sensitivity of radionuclide bone
imaging in determining the presence and
the extent of metastatic disease makes
it an extremely important tool in
disease staging and treatment decisions.
• A primary strength of whole-body bone
scanning is its ability to survey the
entire skeleton on a single study.
• Bone scans usually demonstrate
metastatic lesions much earlier than
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

• Comparing 99mTc-diphosphonate planar


bone imaging with 18F-NaF PET imaging,
most studies have shown a clear
advantage
sensitivity specificity
18F-NaF PET/CT ~ 100% 97%
99mTc-MDPplanar 70% 57%
bone imaging with
SPECT
99mTc-MDPplanar 92% 83%
bone imaging
without SPECT
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

• Some tumors are more likely than others


to produce a false-negative bone scan,
highly aggressive anaplastic tumors,
reticulum cell sarcoma, renal cell
carcinoma , thyroid carcinoma,
histiocytosis, neuroblastoma,
hepatocellular carcinoma, and
especially multiple myeloma.
• 18F-fluorodeoxyglucose(FDG) has higher
sensitivity for lytic lesions than
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

• Patients with asymptomatic tumors that


have a propensity to metastasize to
bone maybe a good case made for
scanning ,e.g., breast, lung, and
prostate
• Tumors with low rates of osseous
metastases may not be cost-effective,
e.g., colon, cervix, uterus, head, and
neck
• Single lesion with proven metastase is
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

• In the rib, if two consecutive ribs are


involved by adjacent discrete foci of
increased activity, the lesions are
almost always secondary to trauma. When
multifocal areas of increased activity
are seen in noncontiguous ribs,
especially if in a linear configuration
along the rib, the likelihood of
metastatic disease is high.
• In the spine, multiple foci of linear
activity in the vertebral bodies more
likely suggest osteoporotic fractures.
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

• In multifocal metastatic disease, the


regional distribution of lesions for
common bone-seeking primary tumors is
as follows: thorax and ribs, 37%; spine,
26%; pelvis, 16%; limbs, 15%; and skull,
6%
• Follow-up bone scans to assess response
in patients undergoing treatment for
advanced breast and prostate cancer
should be interpreted with caution.
bone-seeking tracers may provide an
indirect indication of tumor
improvement through repair of the
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

• Flare phenomenon:after therapy, a


favorable clinical response by focal
bone metastases may result in avid bone
healing through active osteoblastic
repair that causes increased uptake at
involved sites. Usually, it is a good
prognostic sign.
• New bone lesions that appear 6 months
or later after treatment or an interval
increase in activity or the extent of
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

• Superscan: significantly decreased


renal activity with diffusely increased
activity noted throughout the axial
skeleton. diffuse metastases、 primary
or secondary hyperparathyroidism、
hematologic disorders,etc.
• It is also important to look for cold
lesions.
Causes of Cold
Lesions on Bone
Scan
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

• With the widespread use of 18F-FDG


PET/CT in the initial staging and
follow-up of many common malignancies,
bone tracer imaging may not be required
for staging purposes. Bone imaging may
play a significant role in patients in
the absence of definitive 18F-FDG PET
imaging.
• In non–small cell lung cancer (NSCLC),
Some studies have shown that 18F-FDG
PET/CT has as high or higher
sensitivity and specificity than bone
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

• In prostate cancer, bone scans are


highly sensitive in detecting the
typically osteoblastic bone metastases
from prostate cancer. 18F-FDG PET/ CT
has not assumed a major role .18F-NaF
PET/CT bone imaging has been shown to
have superior sensitivity and
specificity to 99mTc-MDP imaging .
Patients with PSA levels ≥20 ng/mL,
Gleason scores ≥8, or locally advanced
disease should undergo radionuclide
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

CASES
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Case1. Multifocal
metastatic disease. A
man who was diagnosed
with NSCLC for 2 years.
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Case2. Multifocal metastatic disease. A


women suffered from breast cancer surgery 2
years later.
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Case3. "hot" lesions with "cold" lesions.


1year after stomach cancer.
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Case4 ."hot" lesions with "cold" lesions.


东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

[Link] scans

diffuse hyperparathyr
metastases oidism
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Malignant Bone Tumors


东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

• Osteogenic sarcoma : appearance


depending on the vascularity and
aggressiveness of the tumor and on the
amount of neoplastic and reactive bone
production ; usually quite intense and
often patchy with photopenic areas;
exact assessment of tumor extent by
bone scanning is often complicated;
because osteosarcomas are bone-forming
lesions, soft-tissue metastases may be
seen as foci of extraskeletal increased
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Osteogenic Sarcoma.
Radiograph (left)
reveals mottled
sclerosis and
periosteal reaction in
the proximal tibia of a
teenager. (Right)
Increased activity is
seen on the bone scan
as well. There is
normal physiologic
activity seen at the
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

• Ewing sarcoma, a relatively common


primary bone tumor, frequently
occurring in the pelvis or femur;
activity is often intense and
homogeneous.
Ewing Sarcoma of
the Left Third Rib.
(A) On the bone
scan, an oblique
view of the ribs
shows abnormal
uptake in the
anterior-lateral
left third rib. (B)
Computed tomography
scan shows the
soft-tissue mass
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Benign Osseous Neoplasms


东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Typical Activity of Benign Bone


Tumors on Bone Scans
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

• An early blood pool image may therefore


be helpful in identifying benign
lesions
• On delayed images, various benign
lesions show a wide range of activity
• Both polyostotic fibrous dysplasia and
Paget disease are sometimes confused
with multifocal metastatic disease
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

(Left) Osteoid Osteoma of


the Left Mid-Tibia. The intense
uptake is characteristic of these
lesions. (Right) Lateral
radiographic tomogram
demonstrates the lesion (arrows)
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Multiple
Enchondromas. (Left) On
the anterior bone scan,
areas of increased
activity are noted,
including in the ribs.
(Right) Rib radiograph
shows a characteristic
expansile lesion with
central matrix (arrows).
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Chondroblastoma. (A)
Whole-body bone scan shows
increased activity in the greater
trochanter of the right hip. (B)
Radiograph shows a lytic lesion
in the same region. (C) Magnetic
resonance imaging scan
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Soft-Tissue Uptake
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

• Soft-tissue activity may be secondary


to any process that evokes soft-tissue
calcification or infarction.
• Soft-tissue neoplasms or their
metastases (especially in the liver)
may calcify, resulting in soft-tissue
activity.
• Radiation therapy may produce increased
chest wall activity in the early weeks
after treatment and, several months
later, may produce relatively decreased
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Causes of Extraosseous Activity


on Bone Scans
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Increased Uptake of Technetium99–Labeled


Bone Imaging Agents in the Kidneys
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Hepatic Uptake of Technetium-99m


Phosphate Compounds
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

CASES
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Liver Metastases. This patient


with a known mucinous colon carcinoma was
thought to have hepatomegaly. (Left) Bone
scan done as part of the workup shows
soft-tissue activity in the right upper
quadrant (arrow). (Right) Subsequent
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Omental Metastases From


Mucinous Ovarian Carcinoma. (A)
Anterior and (B) posterior
whole-body bone scans show
mottled increased activity over
the abdomen. (C) Computed
tomography scan shows that this
is attributable to calcification
in the peritoneal and omental
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Malignant Pleural Effusion. (A)


Anterior (left) and posterior (right)
bone scans show diffusely increased
activity over the left hemithorax.
Nonmalignant effusions uncommonly
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Heterotopic Calcification. This


patient was involved in a motor vehicle
accident 6 months earlier and had a
posterior dislocation of the left hip
without fracture. (Left) Anterior image of
the pelvis from a bone scan now reveals
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Myositis
Ossificans. This college
football player had a
history of trauma to the
inner left thigh with
residual firm swelling
and limitation of motion.
(Left) Bone scan shows
soft-tissue activity
that is greater than the
nearby bone, indicating
that the process is not
mature and should not
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Diffusely Increased
Renal Activity. Posterior
bone scans in the same
patient obtained for
osseous metastases. (Left)
Initial scan demonstrates
the osseous metastases.
(Right) Follow-up scan 2
months later after
vincristine chemotherapy
shows markedly decreased
bone activity and
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Trauma
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

• Fractures not apparent on routine


radiographs may be readily detected
with CT, MRI, or radionuclide bone
scanning
• When multifocal trauma (such as in
child abuse) is suspected, bone
scanning may be more effective.
• Bone scan appearance after fracture may
be divided into acute, subacute, and
healing phases.
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Time After Fracture at Which Bone Scan


Returns to Normal

Time After Fracture at Which


Bone Scan Becomes Abnormal
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

• Subtle trauma, such as that from stress


fractures, is often difficult to
visualize on a plain radiograph. But
three-phase bone scans are usually
positive in all three phases. Bone
scans are an excellent way to diagnose
both fatigue or insufficiency stress
injuries.
• medial tibial stress syndrome, normal
blood flow and normal blood pool are
seen on a three-phase bone scan, On
delayed images, there is typically
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

• Stress fractures tend to be more focal


or fusiform on delayed images and show
increased activity on blood flow and
blood pool phases of a three-phase bone
scan.
• Insufficiency-type stress fractures ,
“Honda sign”
• SPECT or SPECT/CT scans may increase
the sensitivity for detection of occult
fractures, particularly in the spine.
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Occult Fracture of the Left Hip. (A)


Radiograph of the hip does not show
an obvious fracture. However,
anterior bone scan of the pelvis (B)
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Rib Fractures. (A) Anterior and (B)


right lateral images show rib fractures in
this patient who was in an auto accident.
These can be confidently diagnosed because
there are consecutive aligned right rib
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Insufficiency Stress Fracture of the Pelvis. (A)


Posterior delayed image from a bone scan in a 70-year-
old woman with pelvic pain shows an H-shaped area of
increased activity in the sacrum (Honda sign). (B) and
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Pars Defect. A teenager with back


pain was referred for a bone scan. (A) Planar
and (B) Lateral lumbar spine shows the pars
defect (arrow) as well. Post, posterior.
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Stress fractures. Male, 20 years


old, long distance runners with right
leg pain for a week.
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Orthopedic Prosthesis Pain


东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

• Another use of bone scans in trauma is in


the assessment of painful hip or knee
prostheses.
• While sensitive, radionuclide bone tracer
studies are not specific in
distinguishing among the major causes of
prosthesis failure, namely mechanical or
septic (infection), regardless of the
pattern of distribution of activity at
the site of the prosthesis.
• Currently, three-phase and/or delayed
bone scans are best employed as a
screening procedure to determine the need
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Loose Hip Prosthesis. This patient


had bilateral cemented hip
replacements 3 years ago. The
prostheses account for the cold
defects seen in the proximal
femurs on this technetium-99m
methylene diphosphonate image. The
left prosthesis was determined to
be loose, causing increased
activity near the lesser
trochanter and the distal tip of
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Osteomyelitis, Cellulitis, and


Septic Arthritis
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

• At early stage, scanning with


radionuclides often demonstrates
strikingly increased activity, both in
the soft tissues and in the underlying
bony structures. However, if soft-
tissue inflammation is a prominent
feature, it occasionally may be
difficult to distinguish primary bone
involvement from bone activity
secondary to the hyperemia that
accompanies simple cellulitis.
• A number of radiopharmaceuticals are
available to evaluate osteomyelitis.
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

• To differentiate osteomyelitis from


cellulitis on a 99mTcdiphosphonate bone
scan, three-phase scintigraphy has been
widely advocated to improve bone scan
specificity .
• Cellulitis presents as increased blood
flow (perfusion) and diffusely increased
soft tissue on early images, with
decreasing activity on later scans.
• Osteomyelitis, on the other hand,
demonstrates increased blood flow and
blood pool activity with accumulation of
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

• Use of planar 99mTc-MDP for


osteomyelitis has a sensitivity of
greater than 80% and a limited
specificity of about 50%. The
specificity increases to above 80% with
the use of SPECT/CT.
• Septic arthritis is almost always seen
as increased activity in all phases of
a three-phase bone scan.
• Discitis is a condition of uncertain
etiology that usually occurs in
children. On bone scan, there is
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Cellulitis. This drug abuser had pain, redness,


and swelling over the medial aspect of the right ankle.
(A) Soft-tissue swelling was evident on the
anteroposterior radiograph of the ankle. (B) On the bone
scan, there is increased activity on the angiographic
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Osteomyelitis. (A) Plantar images from a


three-phase bone scan show increased flow, increased
blood pooling in the whole foot (B), and increased
intense focal activity on the delayed view in the
region of the right third toe (C). The findings are
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Septic Arthritis. (A)


Three-phase bone scan done on
this young man who had been
bitten over the third
metacarpal joint shows
increased activity (arrow) on
blood pool and (B) delayed
images. (C) Normal radiograph
at the time of the bone scan
became positive 3 weeks later
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Benign Nonneoplastic Disease


东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Paget Disease
• Active Paget disease characteristically
displays a marked increase in activity,
attributable in large part to the
greatly increased regional blood flow
in addition to accelerated bone
turnover. The increased activity
usually conforms to the shape of all or
part of the involved bone. There is
often notable expansion or enlargement
of the bone, and the increased activity
characteristically extends to one end
of the bone when a long bone is
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Paget Disease of the Pelvis. (A)


In this patient, there was an
unexpected finding of expansion
and sclerosis in the left
hemipelvis on barium enema scout
film. (B) Anterior and (C) axial
images from a fluorine-18 sodium
fluoride positron emission
tomography bone scan show
intensely increased activity
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Hypertrophic Pulmonary Osteoarthropathy


• Hypertrophic pulmonary osteoarthropathy
causes regional periosteal reaction,
particularly in the long bones, most
commonly seen in patients with lung
cancer.
• It is may also be associated with other
intrathoracic tumors or nonmalignant
diseases, such as hepatopulmonary
syndrome of advanced liver disease
(cirrhosis) and cyanotic heart diseases.
• The appearance on bone scan is that of
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Hypertrophic Pulmonary
Osteoarthropathy.
A patient with long cancer,
“track sign”
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Metabolic Bone Disease


• Primary hyperparathyroidism due to
hyperfunctioning parathyroid adenomas
and secondary hyperparathyroidism
resulting from renal failure (renal
osteodystrophy) may produce diffusely
increased activity throughout the
skeleton, including the skull, mandible,
and long bones, and relatively
diminished or absent renal activity on
bone scans
• When brown tumors are present, focal
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Avascular Necrosis
• Avascular necrosis most commonly occurs in the
hip, but the shoulders (humeral head), knees,
and ankles may also be affected
• Avascular necrosis of the femoral head is often
a result of trauma, but it may have a variety of
other causes, including slipped capital femoral
epiphysis, steroid use, sickle cell disease,
radiation, and Perthes disease.
• If bone scans are employed, a three phase study
is often performed.
• Decreased or absent activity in the femoral head,
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Avascular Necrosis of the


femoral head.
A patient with long
history of hormone
use,“doughnut appearance”
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Summary

 Radiopharmaceutical
s
 Technique
 Image analysis
 Clinical
Applications
东南大学附属中大医院核医学科
Department of Nuclear Medicine Zhong Da Hospital S outheast University

Thank you !
Radionuclide Therapy

1
What is radionuclide therapy?

 It uses radiation from the decay of radionuclides to treat


diseases.
mainly includes:
 [Link] targeted therapy (radio immunotherapy)
 [Link] interventional therapy (radioactive seed
implantation therapy)
 [Link] application(敷贴)therapy

2
Principle of radionuclide therapy

 Radiopharmaceuticals can be delivered to diseased tissues and


cells by carriers or interventional pathways. And tissues and
cells can actively ingest the drugs. A large number of them are
concentrated in the lesion sites.

 Radiation emitted by radionuclides decay acts on biological


macromolecules (such as nucleic acid and protein), by
breaking up their chemical bonds to change molecular
structure and function, then inhibit and kill diseased cells.

3
Commonly used Radioactive particles

 1. alpha particles
2. beta particles
3. Auger electrons

4
 •Beta-Emitting Radionuclides

 iodine-131 , yttrium-90, samarium-153, strontium-89

 Alpha-Emitting Radionuclides

 bismuth-213,astatine-211,radium-223

 Auger Electron-Emitting Radionuclides

 bromine-77, indium-111,iodine-123, iodine-125

5
Radiopharmaceuticals Applications
Iodine-131(NaI) Graves’ Disease
Thyroid Cancer
32 phosphorus sodium phosphate磷酸钠 Polycythemia(红血球增多症)
89 Strontium (SrCl2) Bone metastases
153 Samarium-EDTMP Bone metastases
I-131 Lipiodol Hepatocellular Carcinoma
131 I -MIBG Pheochromocytoma嗜铬细胞瘤
,NET
111Indium-octreotide neuroendocrine tumors
90 Yttrium- silicate/colloid synovectomy

6
Radiopharmaceuticals Applications

Radioimmunotherapy

90Yttrium-anti-CEA colorectal cancer大肠癌

I-131- Bexxar 托西莫单抗 non hodgkin lymphoma

90Yttrium- Zevalin替伊莫单抗 non hodgkin lymphoma

7
Treatment of Thyroid Diseaes

8
 Oral administration of 131I has been a commonly accepted
procedure for treatment of benign and malignant
conditions of the thyroid since the 1940s.

 The treating physician should be board certified in Nuclear


Medicine, Radiology, or Radiation Oncology and be able to
document equivalent training, competency, and experience
in the safe use and administration of therapeutic amounts
of 131I.

9
 The facility in which treatment is performed must have
appropriate personnel, radiation safety equipments, and
procedures available for waste handling and disposal,
monitoring

 personnel for accidental contamination and controlling


spread of 131I.

10
 The thyroid traps iodine avidly.
 In hyperthyroid states, the percentage of uptake iodine is
usually greater.
 When a suitable radionuclide of iodine is prescribed,
thyroid tissue can be subjected internally to a significant
dose of radiation at low expense to the body.

11
 1311
is the agent of choice for treatment of thyroid
conditions
a. 131I emits beta particles that deposit 90% of their
radiation energy within an area of less than 1 mm
from the decaying radiation atom.
b. Physical half life of 8.04days (enough time to
transport, enough time in stock)
c. easy, safe and simple treatment
d. 131I emits gamma photon that can be measured by
external radiation detectors.
 Therapy means the oral administration of 131I as
sodium iodide to patient in fasting state.

12
Common indication

 Benign Conditions
 Hyperthyroidism

• Graves’ disease

• toxic multinodular goiter

• toxic autonomously functioning thyroid nodules

 Nontoxic goiter
 Well Differentiated Thyroid Cancer (WDTC)

13
Aims of Treatment

 In patients with hyperthyroidism, the aim of treatment with


131I
is to achieve a non-hyperthyroid status, which can be
euthyroid or hypothyroid (replaced by LT4 medication).
 In patients with NTG( nontoxic goiter), the aim of treatment
with 131I is to diminish the size of the goiter and, consequently,
to reduce the symptoms related to gland enlargement and
nodule formation.
 WDTC: postoperative ablation of thyroid remnants

 WDTC: to treat recurrent thyroid cancer and metastatic


disease

14
Absolute Contraindications
 Pregnancy

Radioiodine freely crosses the placenta. The fetal thyroid


concentrates iodine after the 12th week and the radiation will
destroy the thyroid gland and result in severe hypothyroidism.
( Cretinism呆小症)

 activity in the maternal bladder causes significant fetal


irradiation.

 it is recommended that conception be delayed for half a year


after low/ high-dose 131I therapy.

 Breast feeding

 radioiodine are excreted in breast milk

 Not resumed until next pregnancy


15
131I Treatment of Graves' Disease

16
Graves' Disease

 The commonest cause of hyperthyroidism is Graves' disease.


In this condition, the thyroid is diffusely enlarged and traps
more iodine homogeneously.

17
Procedure

1. Patient preparation
 A recent RAIU should be available(Radioactive Iodide
Uptake test )

 The size of the thyroid gland should be estimated,


either by palpation or by some other means(B-
ultrasound , thyroid static imaging)
 Avoidance of interfering of foods/medications
 Pretreatment of selected patients
Routine blood test, liver and kidney function, electrocardiogram

18
 Avoidance of interfering of foods/medications

 All patients must discontinue use of


 iodide containing preparations
 iodine supplements
 thyroid hormones
 other medications that could potentially affect
the ability of thyroid tissue to accumulate iodide
(Kelp, seaweed, Sea fish, scallops, antithyroid
drugs, thyroid hormone )
for a sufficient time before therapy

19
Type of food/medication Recommended time of withdrawal

Antithyroid medication (e.g., propylthiouracil( 3-14 d for antithyroid drugs


丙硫), methimazole(甲硫), carbimazole(甲 7 d for multivitamins*
亢平)) and multivitamins
Natural or synthetic thyroid hormone 10–14 d for triiodothyronine(T3)
3–4 wk for thyroxine(T4)
Kelp, agar, carageen(角叉菜), Lugol’s 2–3 wk, depending on iodide
solution, potassium iodide solution (“SSKI”) content*
Topical iodine (e.g., surgical skin preparation) 2–3 wk*

Radiographic contrast agents 3–4 wk assuming normal renal


Intravenous (water soluble) function
Lipophilic agents (rarely used)静脉亲脂性的 >1 mo
Amiodarone(胺碘酮) 3–6 mo or longer

20
Pretreatment of selected patients

 ATD (抗甲状腺药)to deplete thyroid hormone stores


 thyroid storm危象
 elderly patients and patients with significant pre-existing
heart disease, severe systemic illness, or debility虚弱
 needs to be discontinued for at least 3 d before the
radioiodine therapy is given
 can be resumed 2–3 d after treatment with 131I
 β-blockers can be helpful for symptomatic control.
 need not be discontinued before treatment with 131I.

21
 The treating physician must explain the procedure,
treatment, complications, side effects, therapeutic
alternatives, and expected outcome to the patient. Written
information should be provided to the patient.

 The treating physician must obtain written informed


consent(知情同意) before therapy.

22
 The consent form should include the following items specific to
the therapy of hyperthyroidism:

i. More than one time 131I treatment may be necessary.

[Link] risk of eventual hypothyroidism is high, especially after


treatment of Graves’ disease, and lifelong daily ingestion of a
thyroid hormone tablet would be necessary.

iii. Long-term follow-up will be necessary.

iv. Ophthalmopathy眼病 may worsen or develop after 131I


therapy for Graves’ disease.

23
2. Determination of Administered Activities

 (1)Empiric经验的 dosage strategies (a “fixed” dose)

 (2)calculated dosage strategies

24
 empiric dosage strategies (a “fixed” dose)
 The usual dose prescribed is 10 mCi.

 The advantages are simplicity and successful outcome in


most patients.
 The disadvantage is that some patients receive more 131I
than necessary, and others with large glands or lower
uptake receive insufficient radiation for a single-dose
cure.

25
 calculated dosage strategies

 Initial activity of 80-120 μCi per gram of thyroid is

usually administered

Initial activity (μCi /g)×thyroid weight(g)


Activity of 131I =
24h RAIU

26
 Lower doses reduce the incidence of hypothyroidism
but prolong the time to cure and increase the need for
retreatment.
 higher doses reduce the need to retreat and increase
the incidence of hypothyroidism.
 Hypothyroidism cannot be prevented (it might be the
natural long-term outcome of Graves' disease), and
rapid control of symptoms is advisable.
 It is believed that calculation of the dose to the gland
results in a greater proportion of euthyroid patients.

27
3. Administration : by oral (solution or capsule)

28
4. Side effects/complications –rare
 Acute

 Hypothyroidism

 Ophthalmopathy眼病

29
 Swelling of the goiter Patients with a large goiter may notice
transient swelling of the goiter and dyspnoea呼吸困难, lasts for
approximately 1 week following therapy. A few patients develop mild
pain and tenderness over the thyroid or salivary glands.

 Exacerbation of thyrotoxicosis There may be a transient


rise in free T4 and free T3 levels 7–10 days following radioiodine
treatment, and patients who have been poorly controlled before
radioiodine therapy may experience an exacerbation of heart
arrhythmias心律失常 and heart failure.

 Thyroid storm In some patients a thyroid storm may develop.


This rare condition must be treated with intravenous infusion of ATDs,
corticosteroids 糖皮激素and β-blockers.
30
 Hypothyroidism
 The main side effect of radioiodine treatment is
hypothyroidism ,often considered the expected and
desired outcome of successful therapy can occur within
month or decades later.
 Its rate varies and its incidence continues to increase over
time, so that life-long follow-up is essential.
 LT4 medication is needed in all patients with elevated TSH
after 131I therapy.

31
 Ophthalmopathy
 Prospective randomized controlled trials have shown that
radioiodine treatment is associated with a greater risk of the
appearance or worsening of ophthalmopathy
 Administration of prednisone强的松 helps prevent exacerbation
of ophthalmopathy, and this is now the standard approach in
patients who have clinically active ophthalmopathy at the time of
treatment

32
5. Repeat therapies
 In patients who have not adequately responded to prior 131I

therapy

 usually not indicated until at least 3 months after a radioiodine


treatment to allow the full effect to occur.

 In all cases, 131I therapy may be repeated after a six month


interval if the patient remains biochemically thyrotoxic.

33
6. Radiation precautions

 should not be pregnant or breast-feeding

 no further breast-feeding until the next


pregnancy(6-12 mo. later).

34
 Follow-up should include the following:
—Serum T4 (or T3 in the case of T3 toxicosis) and TSH one month
after therapy;
—Quarterly clinical examination;
—Evaluation of treatment response with serum T3/T4 and TSH six
months after therapy;
—If permanent hypothyroidism develops, hormone replacement
therapy for life.

35
 Toxic nodular goiter and toxic multi-nodular goiter
(Plummer’s disease) are treated by radioiodine therapy as
well.

 The risks in treating the patient with toxic nodules are no


greater than those in treating Graves’ disease and results in
general are quite similar, except for a slightly lower rate of
hypothyroidism.

36
131I Therapy in Thyroid Cancer

37
Thyroid Carcinoma
 Only 5% -10% of thyroid nodules are cancerous.
 There are several types of thyroid cancer.
 Well-Differentiated Thyroid Cancer (WDTC)
 Papillary Carcinoma 乳头状
 Follicular Carcinoma 滤泡状
 Hürthle Cell Carcinoma
 Medullary Carcinoma髓样
 Anaplastic Carcinoma未分化
 Thyroid Lymphoma淋巴瘤

38
 The methods of treatment for thyroid cancer
 Surgery The primary treatment for thyroid carcinoma

 Radioactive iodine treatment


 Thyroid hormone therapy
 External beam radiation therapy
 is not used for cancers that take up iodine
 It is often used to treat anaplastic (未分化)thyroid
cancer.
 Chemotherapy
 is frequently used for anaplastic thyroid cancer
 It is rarely helpful for other types of thyroid cancer

39
 WDTC
 The ability of iodine uptake by WDTC makes 131I
therapy possible
 iodine metabolism in WDTC is altered with decreased
iodine uptake
 WDTC tumors usually continue to express TSH
receptors and will increase iodine uptake under TSH
stimulation

40
 Benefits of 131I Therapy
 Ablate residual microscopic malignancy and tissue destined to
become malignant
 Destroy the normal thyroid tissue to optimize ablative radioiodide
therapy for residual or metastatic disease
 Eliminates the thyroid gland as source of thyroglobulin to facilitate
the follow-up for patients
 Decreases local recurrence
 Improves survival in patients following local recurrence or distant
metastases

41
 Goals of radioiodide therapy in WDTC

1. Ablation of thyroid remnant

2. Treatment of functional residual, metastases,


recurrent thyroid cancer

42
Radioiodine ablation after total or near-total thyroidectomy is a
standard procedure in patients with DTC.
 The only exception is patients with unifocal papillary thyroid
carcinoma ≤1 cm in diameter who lack:
 evidence of metastasis
 thyroid capsule包膜 invasion

 history of radiation exposure


 unfavourable histology组织学: tall-cell, columnar
cell or diffuse sclerosing subtypes.

43
Treatment
 Iodine-avid, non resectable可切除 or incompletely resectable tumour

 radioiodine uptake is scintigraphically proven before therapy

 non resectable or incompletely resectable tumour, e.g. local recurrences,


lymph node metastases or disseminated 播散性的iodine avid lung
metastases or other distant lesions
 Had been shown to be effective in eradicating根除 disease, slowing disease
progression or providing symptomatic relief.

44
Absolute Contraindications

Pregnancy

Breastfeeding

45
1. Patient preparation
 TSH must be elevated >30 IU/ml

 Thyroid hormone withheld at least 2 wk for T3 and 4 to 6


wk for T4
 rhTSH injection
 Low iodine diet for 1-2 weeks prior to treatment
 Avoidance of other interfering factors
 Clinical results should be available and reviewed

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Clinical results should be available and reviewed
 the operative and histology reports (WDTC)

 a baseline serum Tg should be obtained in the hypothyroid


state
 a complete blood count

 a serum calcium or PTH

 Thyroid scan or wholebody scan

 99mTc / 123I / 131I

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2. Administered Activities
 Administered orally
 Prior to administration, the patient should be fasting
 And should abstain from eating for at least 2 hours after
 Dosage selection

Postoperative Ablation of Thyroid Remnants 30–100 mCi

Neck or Mediastinal Lymph Nodes Metastases 150–200 mCi

Distant metastases ≥ 150–200 mCi

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3. Acute Side Effects generally dose related

Side effects treatment

exposure to the bladder & gonads Hydration, frequent urination


sialadenitis sour candies, Vc, (keep in mouth to
increase salivary flow)

neck swelling, dysphagia吞咽困难 glucocorticoid


bone marrow suppression Minimal , Transient , Recovery is
spontaneous
Nausea, vomiting Antiemetics止吐药

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4. Chronic Complications of 131I Therapy
 There is NO increased risk of thyroid tumors and no evidence of
reduced fertility or genetic abnormalities in patients offspring due
to I-131 therapy
 Radiation pneumonitis肺炎 and pulmonary fibrosis may rarely be a
complication in patients with lung metastases. The risk can be decreased
by restricting the whole body retention at 48 hours to less than 80 mCi

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5. Follow up
 Thyroid hormone suppression therapy should be followed
immediately (24h)—LT4

 images of the whole body are obtained 5-10 days after 131I therapy
to ensure targeting.

 Six months to a year after treatment, efficacy should be evaluated


by carrying out a whole body survey with 185 MBq 131I after

hormone withdrawal.

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 Two successive negative whole body studies, with concurrent non-
measurable serum thyroglobulin levels, separated by intervals of
at least six months, indicate successful therapy.
 The patient may then be managed by serum thyroglobulin
estimations twice yearly for five years and then annually for at least
another five years.

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6. Repeated therapy
 Repeated radioiodine therapy if recurrent/persistent

cancer could concentrate 131I (six months after)


 evidenced by a progressive rise in serum thyroglobulin and/or
radiographic evidence of progressive disease.

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Postoperative Ablation of Thyroid Remnants
54
disseminated iodine avid lung metastases

55
M

Treatment of Thyroid Diseases


 The agent of choice for treatment of thyroid disease is 1311
 1311 could be used to treat
 Thyroid benign conditions, include
Graves’ disease, toxic multinodular goiter, toxic autonomously

functioning nodules, and Nontoxic goiter
 And well differentiated thyroid carcinoma
 In treatment of well differentiated thyroid carcinoma, 1311 is used to
 postoperative ablation of thyroid remnants
 to treat recurrent thyroid cancer and metastatic disease

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M

Absolute Contraindications of 1311 therapy:

 pregnancy, breastfeeding
Benefits of 131I Therapy in well differentiated thyroid cancer

 Ablate residual microscopic malignancy and tissue destined to become malignant


 Destroy the normal thyroid tissue to optimize ablative radioiodide therapy for
residual or metastatic disease
 Eliminates the thyroid gland as source of thyroglobulin to facilitate the follow-up
for patients
 Decreases local recurrence or distant metastases

 Improves survival in patients following local recurrence or distant metastases

58
59
 Bone pain is a common complaint in patients with metastases and
often determines quality of life in the later stages of cancer

 About three-quarters of patients with bone metastases have pain.

 Approximately 50% of bone metastases are due to breast,

prostate or lung cancer.

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 The major clinical problem in these patients is pain relief.

 Analgesic止痛 and opiod agents are the first line of treatment for

bone pain in cancer .

 Chemotherapy can also reduce bone pain

 External-beam radiotherapy

 It is particularly useful for local treatment of a solitary


metastatic site or a small number of sites.

61
 Those approach becomes less useful in the context of progressive
skeletal metastases, which result in migratory流动的 multisite
pain.

 severe side effects are very common


 Constipation便秘

 limitations on physical and mental status

 Drug addiction

 Myelosuppression骨髓抑制

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 Palliative 姑息Treatment of Painful Bone Metastases by Radionuclide Therapy
 Treated with ionizing radiation, most common : β-
 Targeted Therapy
 Bone-Seeking Radiopharmaceuticals
 toxicity of systemic administration is reduced
 Palliative Treatment
 this is not a curative treatment for cancer but a treatment to palliate减
轻 pain, even though some cancer cells may be killed
 Acting systemically, radionuclide therapy is well suited to the
management of disseminated传播 disease

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 The mechanism of bone pain palliation by ionizing
radiation is poorly understood.

 Radiation-induced humoral changes within normal


osteocytes and in the surrounding microenvironment

may be an important mechanism in symptom relief.

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 Bone targeting
 relies on selective uptake and prolonged retention at sites of

increased osteoblastic 成骨activity.

 Some therapeutic radionuclides, such as 89Sr (Strontium) have

a natural affinity for metabolically active bone.

 Others, including Samarium and Rhenium, form stable

complexes with bone-seeking cations, such as phosphate and


diphosphonate.

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 The radiopharmaceuticals used for palliation of
metastatic bone pain
 Phosphate-32

 Strontium-89

 Samarium-153

 Rhenium-186

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 89Sr(Strontium-89)

 emits β particle

 average soft-tissue range 2.4 mm

 It has a 50.5-d physical half-life

 chemically similar to calcium , follows the biochemical pathways of

calcium in the body, and incorporated into the hydroxyapatite


molecule in bone

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 89Sr(Strontium-89) therapy means the intravenous
injection of the radionuclide as strontium
chloride(SrCl2).

 Usual therapeutic administered activity is 1.5–2.2

MBq/kg (40–60 μCi/kg) or 148 MBq (4 mCi).

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 153Sm (Samarium-153)

 emits β particle
 average soft-tissue range 0.6 mm
 It has a 1.9-d physical half-life
 153Sm therapy means the intravenous injection of 153Sm-EDTMP targets

hydroxyapatite at sites of increased osteoblastic activity成骨活性


 Usual therapeutic administered activity is 1 mCi/kg.

(153Sm chelated to Ethylene Diamine TetraMethylene Phosphonate ).

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 Before administration of 89Sr-chloride or 153Sm-EDTMP, the patient
should have had recent bone scintigraphy (less than 8 wk)
documenting increased osteoblastic activity in the painful sites.

 The patient need not fast before administration of the


radiopharmaceutical.

 Hospitalization is not required

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 The radiopharmaceutical should be administered slowly through an
intravenous catheter(静脉内导管) and a running intravenous line to
avoid infiltration, to reduce the hand dose to the injecting physician,
and to permit flushing of the syringe so that all of the 89Sr-chloride
and 153Sm-EDTMP is injected.

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 The best candidates for radionuclide palliative therapy
1. patients with advanced cancer who have more than one bone metastatic
lesion and are not candidates for, or are refractory to, conventional
analgesic medical treatments(不适合传统止痛药治疗).
2. The abnormal bone scan indicates increased osteoblastic activity
3. Patients should have an estimated life expectancy of at least 3 months
4. platelet count > 80×109/L
leukocyte count > 3.5×109/L

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1. Patients with pain from other causes
2. 6 weeks before or following myelosuppressive chemotherapy
3. Pregnant patients are not candidates for therapy
4. Patients with impending spinal cord (脊髓)compression or impending
long bone fractures as evidenced by greater than 50% cortical erosion
5. Patients with severe renal failure (GFR less than 30 mL/min)

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 A systematic review of published data reported pain relief in
approximately 74% of patients
 Most patients note pain relief in 2-3 (maximum 6) weeks and the
average response time is 4-15 months.

 Treatment can be repeated safely for recurrent pain

 The procedure may be repeated 12 or more wk after the first


injection if blood counts are at the suggested levels.

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A. “Pain Flare” phenomenon
 In some patients, transient worsening of bone pain may occur
within several days (most often within 3d ) of injection and
last several days (2–5 d).

 “Pain Flare” can be treated by increasing doses of analgesia, if


required.

 flare phenomena are associated with good clinical response

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B. Hematologic Toxicity(血液毒性)
 Mild myelosupression is seen in about 80% of patients

 A decrease of thrombocytes and leucocytes count in peripheral


blood, as a result of myelosuppression, is frequently observed and
has a nadir (最低点)of 3–5 weeks (153Smlexidronam) or 12–16
weeks (89Sr).
 Patients blood counts should be monitored weekly.

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Palliative Treatment of Painful Bone Metastases
 Most common radionuclides used
89SrCl 153Sm-EDTMP
 2,

 Pain Flare

 Common Indications(4)

 Contraindications(5)

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