Lectures on Medical Biophysics

Department of Biophysics, Medical Faculty,

Masaryk University in Brno
Lectures on Medical Biophysics
Department of Biophysics, Medical Faculty,
Masaryk University in Brno

Nuclear medicine and radiotherapy

Nuclear medicine and radiotherapy

In this lecture we deal with selected methods of nuclear

medicine and radiotherapy including their theoretical
background:
Radioactive decay
Interactions of ionising radiation with matter
Biological effects of ionising radiation
Nuclear medicine
➢Simple metabolic examinations
➢Imaging
Radiotherapy
➢Sources of radiation – radioactive and non-radioactive
➢ Methods of radiotherapy

3
 Radioactivity
• Radioactivity or radioactive decay is the
spontaneous transformation of unstable nuclei into
mostly stable nuclei. This is accompanied by the
emission of gamma photons, electrons, positrons,
neutrons, protons, deuterons and alpha particles. In
some transformations, neutrinos and antineutrinos
are produced. Unstable nuclei can be found
naturally or created artificially by bombarding
natural stable nuclei with e.g. protons or neutrons.
• Radioactive decay has a stochastic character: it is
not possible to determine which nucleus will decay
at what time (tunnel effect).
4
Radioactive decay

Laws valid for radioactive decay

➢Law of mass-energy conservation

➢Law of electric charge conservation
➢Law of nucleon number conservation
➢Law of momentum conservation
➢……………………

5
Radioactive decay

Law of radioactive decay

The activity A of a radioactive sample at a given time (i.e,
the number of nuclei disintegrating per second, A = dN/dt)
is proportional to the total number of undecayed nuclei
present in the sample at the given time:

 is the decay or transformation constant

Units of A are becquerel (Bq) [disintegrations per second, s-1]
(in the past: curie, 1 Ci = 3.7·1010 Bq)

The negative sign indicates that the number of undecayed nuclei is

decreasing.
6
Radioactive decay

This equation is solved by integration:

Nt = N0·e-.t

A more useful equation for nuclear medicine

and radiotherapy is (obtained by dividing the
above equation by dt on both sides):

At = A0·e-t A is activity

7
Radioactive decay

Physical half-life

➢Tp – time in which the sample activity At

decreases to one half of the initial value
A0. Derivation:
A0/2 = A0·e-Tp thus ½ = e-Tp
➢taking logarithm of both sides of the
equation and rewriting:
Tp = ln2/p thus Tp = 0.693/p
8
Radioactive decay

Biological and effective half-life

➢ Tb – biological half-life – time necessary for the

physiological removal of half of a substance from
the body
➢ b – biological constant – relative rate of a
substance removal
➢ Biological and physical processes take place
simultaneously. Therefore, we can express the Tef –
effective half-life and
ef – effective decay constant
➢ The following equations hold: ef = b + p and
1/Tef = 1/Tp + 1/Tb ,
thus
9
Radioactive decay

Technetium generator
During radioactive decay, a daughter radionuclide is
produced. In cases when the half-life of the parent
radionuclide is much longer than the half-life of the daughter
radionuclide both parent and daughter end up with the same
activity (radioactive equilibrium).

 1N 1 =  2N 2
An example of practical
importance of the
radioactive equilibrium in
clinical practice –
production of technetium
for diagnostics: Mo-99
half-life is 99 hrs., Tc-99m
half-life is 6 hrs.
10
Radioactive decay

Classes of radioactive decay

a (alpha) decay

Seaborgium transforms in rutherfordium. Helium nucleus

– a particle – is liberated. Daughter nucleus recoils as a
consequence of the law of momentum conservation.
(http://www2.slac.stanford.edu/vvc/theory/nuclearstability.html)
11
Radioactive decay

Classes of radioactive decay

b decay is an isobaric transformation in which besides the b particles
are formed also neutrinos (electron antineutrino or electron neutrino
ne)

b (beta) decay = emission

of an electron or positron K-capture
12
Radioactive decay

Classes of radioactive decay

 (gamma) decay
Transformation of
dysprosium
nucleus in
excited state

The other classes of radioactive decay:

➢ Emission of proton, deuteron, neutron …
➢ Fission of heavy nuclei

13
Interaction of ionising radiation with
matter
➢ The interaction of radiation with matter is usually
accompanied by the formation of secondary radiation
which differs from the primary radiation by lower energy
and often also by kind of particles.
➢ Primary or secondary radiation directly or indirectly
ionises the medium, and creates also free radicals.
➢ A portion of the radiation energy is always transformed
into heat.
➢ The energy loss of the particles of primary radiation is
characterised by means of LET, linear energy transfer,
i.e. energy loss of the particle in given medium per unit
length of its trajectory. The higher the LET the more
damaging is the radiation to tissues and the higher the
risk from the radiation.
14
Interaction of ionising radiation with matter

Attenuation of X / gamma radiation

When a beam of X or gamma radiation passes through a substance:
absorption + scattering = attenuation
A small decrease of radiation intensity -dI in a thin substance layer is
proportional to its thickness dx, intensity I of radiation falling on the layer,
and a specific constant m:
-dI = I.dx.m
After rewriting:
dI/I = -dx.m
After integration:
I = I0·e-mx
I is intensity of radiation passed through the layer of thickness x, I0 is the
intensity of incident radiation, m is linear coefficient of attenuation [m-1]
(depending on photon energy, atomic number of medium and its density).
15
Interaction of ionising radiation with matter
Interactions of photon radiation (X-rays
and gamma rays)
➢ Photoelectric effect and Compton scattering – see the lecture on X-
ray imaging.
➢ Electron - positron pair production (PP) – very high energy photons
only. The energy of the photon is transformed into mass and kinetic
energy of an electron and positron. The mass-energy E in each particle
is given by:
E = m0 c2 (= 0.51 MeV),
m0 is rest mass of an electron / positron (masses of electron and
positron are equal), c is speed of light in vacuum. Energy of the photon
must be higher than twice the energy calculated using the above formula
(1.02 MeV). We can write:
E = hf = (m0c2 + Ek1) + (m0c2 + Ek2)
➢ Terms in brackets: mass-energies of created particles, Ek1 a Ek2 kinetic
energies of these particles.
➢ The positron quickly interacts (annihilates) with any nearby electron, and
two photons originate, each with energy of 0.51 MeV. 16
Interaction of ionising radiation with matter

Electron - positron pair production

17
Interaction of ionising radiation with matter

Interaction of corpuscular radiation with

tissue
➢b radiation = fast electrons or positrons – ionise the medium as in X-
ray production. Trajectory of a b particle is several millimetres in
aqueous medium.

➢a radiation ionises directly by impacts. There is formed big number of

ions along its very short trajectory in medium (mm) – so it loses energy
very quickly along a short trajectory (= very high LET) .

➢Neutrons ionise by elastic and non-elastic impacts (scatter) with

atomic nuclei. The result of an elastic scatter differs according to the
ratio of neutron mass and atom nucleus mass. When a fast neutron
hits the nucleus of a heavy element, it bounces off almost without
energy loss. Collisions with light nuclei lead to big energy losses. In
non-elastic scatter, the slow (moderated, thermal) neutrons
penetrate into the nucleus, and if they are emitted from it again, they do
not have the same energy like the incident neutrons. They can lead to
the emission of other particles or fission of heavy nuclei.
18
Interaction of ionising radiation with matter
Main quantities and units for
measurement of ionising radiation
➢Absolute value of particle energy is very small. Therefore, the electron
volt (eV) was introduced. 1 eV is the kinetic energy of an electron
accelerated from rest by electrostatic field of the potential difference 1
volt.
1 eV = 1.602·10-19 J.
➢Energy absorbed by the medium is described by absorbed dose (D) -
unit gray, Gy). It is the amount of energy absorbed per unit mass of
tissue. Gray = J·kg-1
➢Dose rate expresses the absorbed dose in unit time [J·kg-1·s-1]. The
same absorbed dose can be reached at different dose rates during
different time intervals.
➢The radiation hazard to biological objects depends mainly on the
absorbed dose and the type of radiation. The radiation weighting factor
is a number which indicates how hazardous a type of radiation is (the
higher the LET the higher the radiation weighting factor).
➢Equivalent dose De is defined as the product of the absorbed dose and
the radiation weighting factor. The unit of Equivalent dose is the sievert
(Sv).
➢Effective dose (Sv) – kind of irradited tissue is also taken into account.19
Biological effects of ionising radiation

➢ Physical phase – time interval of primary effects. Energy of

radiation is absorbed by atoms or molecules. Mean duration
is about 10-16 s.
➢ Physical-chemical phase – time interval of intermolecular
interactions (energy transfers). About 10-10 s.
➢ Chemical (biochemical) phase – free radicals are formed.
They interact with important biomolecules, mainly with DNA
and proteins. About 10-6 s.
➢ Biological phase – a complex of interactions of chemical
products on various levels of the living organism and their
biological consequences. Depending on these levels, the
duration ranges from seconds to years.
20
Biological effects of ionising radiation
➢ Direct action (hits) – physical and physical-chemical
process of radiation energy absorption, leading directly
to changes in important cellular structures. It is the most
important action mechanism in cells with low water
content. Theory of direct action is called target theory. It
is based on physical energy transfer.

➢ Indirect effects are mediated by water radiolysis

products, namely by free radicals H* a OH*. It is most
important in cells with high water content. The free
radicals have free unpaired electrons which cause their
high chemical reactivity. They attack chemical bonds in
biomolecules and degrade their structure. Theory of
indirect action – radical theory – is based on chemical
energy transfer.
21
Biological effects of ionising radiation

Effects on the cell

In proliferating cells we find these levels of
radiation damage:

➢ Transient stopping of proliferation

➢ Reproductive death of cells (vital functions are
maintained but proliferation ability is lost)
➢ Instantaneous death of cells

Cell sensitivity to ionising radiation

(radiosensitivity), or their resistance
(radioresistance) depends mainly on the repair
ability of the cell.
22
Biological effects of ionising radiation

Effects on the cell

Factors influencing biological effects in general:

➢ Physical and chemical: equivalent dose, dose rate,

temperature, spatial distribution of absorbed dose, presence of
water and oxygen.
➢ Biological: species, organ or tissue, degree of cell
differentiation, physiological state, spontaneous ability of repair,
repopulation and regeneration.
Sensitivity of cells is influenced by:
➢ Cell cycle phase (S-phase!)
➢ Differentiation degree. Differentiated cells are less sensitive.
➢ Water and oxygen content. Direct proportionality (+,+)
Very sensitive are e.g. embryonic, generative, epidermal, bone
marrow and also tumour cells
23
Biological effects of ionising radiation

Tissue sensitivity
Arranged according to the
decreasing radiosensitivity:
lymphatic Typical symptoms of radiation
spermatogenic epithelium of testis sickness:
bone marrow 1. Non-lethal – damage to the
gastrointestinal epithelium erythropoiesis (bone marrow),
ovaries effects on gonads
cells of skin cancer 2. Lethal – gastrointestinal
connective tissue syndrome (damaged
liver epithelium), skin burning,
pancreas damage to suprarenal glands,
kidneys damaged vision, nerve
syndrome (nerve death)
nerve tissue
brain Late sequels – cumulative –
genetic damage, cancer
muscle 24
Nuclear medicine

Nuclear medicine
➢Simple metabolic examinations
➢Imaging

25
Nuclear medicine
Scintillation counter and scintigraphy
(history of medicine)
➢ Scintillation counter consisted of a scintillation detector, mechanical
parts and a lead collimator. The collimator enabled the detection of
radiation only from a narrow spatial angle, in which the examined body
part was located. Signals of the detector were amplified, counted and
recorded.
➢ Scintigraphy was used mostly for examination of kidneys and thyroid
gland – by means of gamma-emitters: iodine-131 or technetium-99m.
Tc-99m has a short half-life (6 hours vs. 8 days in I-131). Technetium is
prepared directly in dept. of nuclear medicine in technetium
generators.
➢ Iodine used for thyroid was administered as KI, for kidneys was used
technetium-labelled DTPA (diethylen-triamin-penta-acetic acid). Tc-99m
is almost an ideal diagnostic radionuclide – fastly excreted, short half-
life, almost pure gamma rays. (Iodine-131 produces also b-particles
which increases radiation dose without any benefit). Recently, I-123 with
half-life of 13.27 hours is also used in SPECT.

26
 The Gamma Camera

MCA

photomultiplier
tubes
(now being
replaced by a flat
digital sensor) thin
(about 1.5
parallel hole
cm) NaI
Pb
phosphor
collimator
crystal
for
localisation 28
Nuclear medicine

Gamma-camera
➢ The digital sensor / photomultiplier signals carry
information about the position of the scintillation
events. However, a defined point on the crystal
has to correspond with defined point of the
examined body part – we obtain an image of
radionuclide distribution in the body. This can be
achieved only by collimators.

➢ Anger cameras show the radionuclide distribution

very quickly. Therefore they can be used for
observation of fast processes, including blood
flow in coronary arteries. They can also move
along the body. Physiologic (functional)
information is obtained or metastases found (if
the radionuclide is entrapped there - iodine-131 A whole body scan
or technetium-99m).
showing metastases
of a bone tumour
29
Nuclear medicine

SPECT – single photon emission

computed tomography

• Photons of radiation are detected from various

directions, which allows reconstruction of a
cross-section.
• Most frequent arrangements and movements
of detectors:
➢ Anger scintillation camera revolves around the
body.
➢ Many detectors are arranged around the body in a
circle or square. The whole system can revolve
around the body in a spiral (helix).
30
Nuclear medicine

Principle of SPECT

In SPECT, common
sources of radiation
(iodine-131,
technetium-99m) are
used.

An object with a radiation source Z is surrounded by

scintillation detectors F with collimators K. The collimators
allow detection only of gamma-rays falling normally onto the
detector blocks. It enables us to localise the source of rays.
31
Nuclear medicine

SPECT – images
http://www.physics.ubc.ca/~mirg/home/tutorial/applications.html#heart

Perfusion of heart in different

planes. „Hot“ regions are well
blood supplied parts of the heart

Brain with „hot“

regions

32
Nuclear medicine
PET - positron emission tomography
➢ In PET, positron emitters are used. They are prepared in
accelerators, and their half-lives are very short – max. hours.
For that reason the examination must be done close to the
accelerator, in a limited number of medical centres.
➢ The positrons travel only very short distance, because they
annihilate with electrons forming two gamma photons (0.51
MeV), which move in exactly opposite directions. These
photons can be detected by two opposite detectors connected
in a coincidence circuit. Voltage pulses are recorded and
processed only when detected simultaneously in both
detectors. Detectors scan and rotate around the patient's body.
➢ The spatial resolution of PET is substantially higher than in
SPECT. The positron emitters are attached to e.g. glucose
derivatives, so that we can obtain also physiological
(functional) information. PET of brain visualises those brain
centres which are at the moment active (have increased uptake
of glucose). PET allows to follow CNS activity on the level of33
brain centres.
Nuclear medicine

PET principle

More realistic scheme

Explanation of the high spatial resolution of PET: The opposite

detectors in a coincidence circuit. A source of radiation Z is detected only
when lying on a line connecting the detectors. Detector A but not the
detector B can be hit through a collimator from the source Z2, because
this source is outside the detection angle of B. In SPECT, the signal
detected by A from Z1 would be partially overlapped by the signal coming
from source Z2. 34
Nuclear medicine
Functional PET of brain
http://www.crump.ucla.edu/software/lpp/clinpetneuro/lggifs/n_petbrainfunc_2.html

resting

Music – a non-verbal
acoustic stimulus
Visual stimulus
35
Nuclear medicine

intensive thinking

remembering a
picture

skipping on left leg

36
Nuclear medicine

Brain tumour - astrocytoma

FDG – fluorodeoxyglucose, F-18

37
Radiotherapy

➢ Sources of radiation
– radioactive
- non-radioactive
➢ Methods of radiotherapy

38
Radiotherapy

Sources of radiation - radioactive

➢Artificial radionuclides are used. The source is in direct contact
with a tissue or is sealed in an envelope (open or closed
sources).
➢The open sources:
– (1) Can be applied by metabolic way. Therapy of thyroid gland tumours
by radioactive iodine I-131, which is selectively captured by the thyroid.
– (2) Infiltration of the tumour by radionuclide solution, e.g. a prostate
tumour by the colloid gold Au-198. This way of application is seldom
used today as well.
➢The closed sources are more widely used today:
– (1) Needles with a small amount of radioactive substance. They usually
contain cobalt Co-60 or caesium Cs-137. The needles are applied
interstitially (directly into the tumour).
– (2) The sources are also inserted into body cavities (intracavitary
irradiation - afterloaders).
– (3) Large irradiation devices (‘bombs’) for teletherapy. The radionuclide
is enclosed in a shielded container. The radioactive material is moved
into working position during irradiation. The most commonly used are
cobalt Co-60 or caesium Cs-137. These devices are obsolete today. 39
Radiotherapy

„The cobalt bomb“

In 1951, Canadian Harold E. Johns used cobalt-60 for therapy

first.

40
Radiotherapy

„The cobalt bomb“

http://www.cs.nsw.gov.au/rpa/pet/RadTraining/

41
Radiotherapy

Leksell Gamma Knife (still used)

➢ 1951 – idea of radiosurgery by L. Leksell of Sweden
➢ The Leksell Gamma Knife is used for treatment of some
brain tumours and other lesions (aneurysms, epilepsy etc.)
➢ 201 Co60 sources are placed in a central unit with diameter of
400 mm in 5 circles, which are separated by the angle of 7.5
degree. Each beam is collimated by a tungsten collimator
with a conical channel and a circular orifice (4, 8, 14 a 18 mm
in diameter). The focus is in the centre where all the channel
axes (beams) intersect. The beams converge in the common
focus with accuracy of 0.3 mm.
➢ The treatment table is equipped by a movable couch. The
patient‘s head is fastened in the collimator helmet. It is
attached to the couch, which can move inside the irradiation
area.
42
Radioterapie

Leksell Gamma Knife

http://www.nrc.gov/images/reading-
rm/photo-gallery/20071114-040.jpg
Radiotherapy

Leksell Gamma Knife

➢ A Leksell stereotactic coordinate frame is attached to

patient‘s head by means of four vertical supports and
fixation screws. The head is so placed in a 3D
coordinate system, where each point is defined by
coordinates x, y, z. Their values can be read on the
frame. The target area can be located with an accuracy
better than ± 1 mm.

➢ A radiological image of the lesion is transferred to the

planning system which calculates the total dose from all
the 201 sources. By connecting of points with the same
dose a curve – isodose – is constructed. The borders of
treated lesion should correspond with isodose showing
50-70% of dose maximum. The isodoses copy precisely
the outlines of the pathologic lesion in tomographic
scans. 44
Radiotherapy

Leksell Gamma Knife

45
Radiotherapy
Leksell Gamma Knife

46
Radiotherapy

Afterloader
works with Ir-192. An instrument for safe intracavitary irradiation.

applicators
Control unit
main unit
phantom

47
Radiotherapy

Radiation sources – non-radioactive

A) X-ray tube devices: Therapeutic X-ray tubes differ in construction
from diagnostic X-ray tubes. They have larger focus area, robust
anode and effective cooling. They are (were) produced in three
sorts:
– low-voltage (40 - 100 kV) for contact surface therapy. The
radiation is fully absorbed by a soft tissue layer 2 - 3 cm thick.
e.g., Chaoul lamp.
– medium-voltage (120 - 150 kV) for brachytherapy – from
distance of max. 25cm. They were used to irradiate tumours at
max depth 5 cm.
– ortho-voltage (160 - 400 kV) for teletherapy (deep irradiation
from distance). These have been replaced by the radionuclide
sources and accelerators.
B) Electron Accelerators: X-rays with photon energy above 1 MeV
and -radiation with photon energy above 0.66 MeV are used for
megavoltage therapy. Their sources are mainly electron
accelerators. The accelerated electrons are usually not used for
direct irradiation but the production of high-energy X-rays.
48
Radiotherapy

The linear accelerator

CLINAC 2100C in Masaryk memorial institute of oncology in Brno

49
Radiotherapy

The linear accelerator

http://www.cs.nsw.gov.au/rpa/pet/RadTraining/MedicalLinacs.htm

50
Radiotherapy

The cyclotron
Z – source of the
accelerated particles
(protons),
D1 and D2 – duants or
dees,
G - generator of high-
frequency voltage.

51
Radiotherapy

The cyclotron
http://www.aip.org/history/lawrence/first.htm

1933 – one
of the first
cyclotrons in
background

Ernest O. Lawrence
(1901-1958)
52
Radiotherapy

The cyclotron in
oncology – proton
(hadron) therapy

The Sumitomo cyclotron

53
Radioterapie
Hadron radiotherapy
Hadrons (protons and light ions) lose their energy mainly in collisions
with nuclei and electron shells. The collisions with electrons are dominant
for energies used in radiotherapy. The energy deposited is indirectly
proportional to the second power of hadron velocity. It means practically
that the hadrons deposit most of their energy shortly before end of their
tracks in the tissue. This fact is exploited in hadron therapy because (in
contrary to the conventionally used photons) the tissues lying in front of
the Bragg peak receive a much smaller dose compared with the target
area. The tissues behind the target are not irradiated. The target can be
precisely determined and thus damage to the surrounding healthy tissue
is minimised. The Bragg peak area is given by energy of the particle. In
therapy, the necessary penetration depth is about 2 – 25 cm, which
corresponds to an energy of 60 – 250 MeV for protons and 120 – 400
MeV for light ions.

54
Radioterapie

Radiotherapy planning for X-ray beams

After tumour localisation, the radiotherapist determines the best way of

irradiation in co-operation with a medical physicist. The tumour has to
receive maximum amount of radiation but the healthy tissues should be
irradiated minimally and some should be totally avoided. When
irradiating the tumour from only one side, the tissues in front of it would
receive higher dose than the tumour and the near side of the tumour
more than the far one. That is why irradiation is performed from different
directions. The skin area, through which the radiation beam enters the
body, is called the irradiation field; irradiation from different directions
(2, 3, 4) is called multi-field treatment. In some cases (tumours of
oesophagus and prostate) the multi-field treatment is replaced by
moving beam treatment – the source of radiation moves above or
around the patient in circle or arc (tumour-centred) during irradiation.
The radiotherapeutic plan involves the energy of radiation, daily and
total dose of radiation, number of fractions etc.
55
Radioterapie

Simulator
X-ray simulator is an XRI device
having the same geometry as
the accelerator. It is used to
locate the target tissues which
should be irradiated. To ensure
always the same patient
positioning both in the simulator
and the accelerator, there is a
system of laser lights in the
room. An identical system of
laser beams is used in the
accelerator room.
Radiotherapeutic simulator Acuity 56
Radiotherapy

Geometry of irradiation
For irradiation of surface tumours, we have to use radiation of low
energy, for deep tumours, the energy must be substantially higher.
In radiotherapy, mainly X-ray sources are used (the accelerators for the
so-called megavoltage therapy) as well as the cobalt-60 -radiation
sources. The radiation dose is optimised by means of simulators. To
achieve maximum selectivity of deep tumour irradiation, the
appropriate irradiation geometry must be applied:

➢ Focal distance effect. Intensity of radiation decreases with the

square of source distance. The ratio of surface and deep dose is
higher when irradiating from short distance. Therefore, surface lesions
are irradiated by soft rays from short distances (contact therapy,
brachytherapy). Deep tumours are treated by penetrating radiation
from longer distance (teletherapy).

➢ Irradiation from different directions or by a moving source. The lesion

must be precisely localised, the irradiation conditions must be
reproducible. Advantage: The dose absorbed in the lesion (tumour) is
high – radiation beams intersect there. Dose absorbed in surrounding
tissue is lower. 57
Radiotherapy

Geometry of irradiation

The effectiveness of
repair processes in
most normal tissues is
higher than in tumours.
Therefore, partition
(fractionation) of the
therapeutic dose in
certain number of
fractions or use of
„moving beam „moving beam
treatment“ spares the treatment“
normal tissue.
58
Authors:
Vojtěch Mornstein, Ivo Hrazdira

Content collaboration and language revision:

Carmel J. Caruana

Presentation design:
Lucie Mornsteinová

Last revision: December 2018