TOPIC 2

BASICS RADIOBIOLOGY FOR

RADIOTHERAPY
(2 hours)
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 2.1 Introduction
2.2 Radiation Chemistry
2.3 Volume Definition
2.3.1 Gross Tumour Volume (GTV)
2.3.2 Clinical Target Volume (CTV)
2.3.3 Planning Target Volume (PTV)
2.3.4 Treated Volume (TV)
2.3.5 Irradiated Volume (Iv)
2.3.6 Organs At Risk (Oar)
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 2.4 5 Rs
2.4.1 Repair
2.4.2 Repopulation
2.4.3 Reoxygenation
2.4.4 Redistribution
2.4.5 Radiosensitivity
2.5 Biological Effect of Ionizing Radiation
2.5.1 Dose Response Curve
2.5.2 Cell Survival Curve
2.5.3 Systemic Effects
2.5.4 Oxygen Effect
2.5.5 LET
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2.5.6 Relative Biological Effectiveness (RBE)
Dr. Nik Noor Ashikin Bt Nik Ab Razak 3
 2.1 Introduction

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 2.1 Introduction
ACTION Of radiation
ionizing physics
radiation on Radiobiology
biological +
tissues biology

radiation
INTERACTIONS
between Ionizing
physics Radiation
radiation and +
living systems
oncology
biology
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 2.1 Introduction
Total dose and
number of fractions

Radiobiology allows the

optimization of a radiotherapy
schedule for individual patients
Tumour control in regards to:
probability (TCP) and Overall time of the
normal tissue radiotherapy
complication
course
probability (NTCP)
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 2.2 Radiation Chemistry

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 2.2 Radiation Chemistry
1) DIRECT ACTION

Radiation may impact the DNA directly, Dominant process in the

causing ionization of the atoms in the DNA interaction of high LET
molecule (“direct hit”). It is a fairly uncommon particles such as neutrons or
occurrence due to the small size of the target; the alpha particles with biological
diameter of the DNA helix =2 nm. material.

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 2.2 Radiation Chemistry
2) INDIRECT ACTION
This results in the
The radiation interacts production of free
with non-critical target radicals, which are atoms
atoms or molecules, or molecules that have an
usually water. unpaired electron and
thus are highly reactive
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These free radicals can
then attack critical targets
such as the DNA. Damage
from indirect action is
much more common than
damage from direct action
9
 2.2 Radiation Chemistry

• Indirect action: Electrons

produce free radicals which
break chemical bonds and
produce chemical changes

• Direct Action: Photon ejects

an electron which produce a
biological damage on the
DNA
2.2 Radiation Chemistry
2.2 Radiation Chemistry
 2.3 Volume Definition
2.3.1 Gross Tumour Volume (GTV)
2.3.2 Clinical Target Volume (CTV)
2.3.3 Planning Target Volume (PTV)
2.3.4 Treated Volume (TV)
2.3.5 Irradiated Volume (Iv)
2.3.6 Organs At Risk (Oar)
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 2.3 Volume Definition
• Volume definition is a prerequisite for meaningful 3-D treatment
planning and for accurate dose reporting.
• ICRU reports No. 50 and 62 define and describe several target and critical
structure volumes that aid in the treatment planning process and that
provide a basis for comparison of treatment outcomes.
• The following volumes have been defined as principal volumes related to
3-D treatment planning: gross tumour volume (GTV), clinical target
volume (CTV), internal target volume (ITV) and planning target volume
(PTV)
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2.3 Volume Definition

GTV – Gross Tumour Volume

CTV – Clinical Target Volume

PTV – Planning Target Volume

OAR – Organ at Risk

TV – Treated Volume

IV – Irradiated Volume
 2.3.1 Gross Tumour Volume (GTV)

The gross palpable, visible

and demonstrable extent and
location of the malignant
growth (ICRU Report No. 50)
 2.3.1 Gross Tumour Volume (GTV)
• This is determined by physical examination by the oncologist and the
results of radiological investigations relevant to the site of the tumour.

• As the term suggests, tumours have a length, breadth and depth, and
the GTV must therefore be identified using orthogonal 2D or 3D
imaging (computed tomography (CT), magnetic resonance imaging (MRI),
ultrasound, etc.), diagnostic modalities (pathology and histological reports, etc.)
and clinical examination.
 Gross Tumour Volume (GTV)
– Gross palpable or visible/demonstrable
extent and location of tumour
GTV

Part VIII.3.7 Operational Considerations – Planning of physical Slide 19

treatment
 2.3.2 Clinical Target Volume (CTV)
•“The clinical target volume (CTV) is the
tissue volume that contains a
demonstrable GTV and/or sub-clinical
microscopic malignant disease, which has
to be eliminated. This volume thus has to
be treated adequately in order to achieve
the aim of therapy, cure or palliation”
(ICRU Report No. 50)
 2.3.2 Clinical Target Volume (CTV)
• Usually determined by the radiation oncologist, often after
other relevant specialists such as pathologists or radiologists
have been consulted.

• This volume may not be defined separately but considered when

defining the planning target volume (PTV) (e.g. CTV = GTV + 1
cm margin)
 Clinical Tumour Volume (CTV)
CTV Contains a GTV and/or sub-clinical
microscopic malignant disease, which has to
be eliminated CTV

Part VIII.3.7 Operational Considerations – Planning of physical Slide 22

treatment
 2.3.3 Planning Target Volume (PTV)
•“The planning target volume (PTV) is a
geometrical concept, and it is defined to
select appropriate beam arrangements, taking
into consideration the net effect of all possible
geometrical variations, in order to ensure that
the prescribed dose is actually absorbed in the
CTV” (ICRU Report No. 50)
 2.3.3 Planning Target Volume (PTV)

• The PTV includes the internal target margin (ICRU Report No.
62) and an additional margin for the set-up uncertainties,
machine tolerances and intratreatment variations

• It fully encompasses the GTV and CTV (e.g : PTV = CTV + 1

cm).

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 2.3.3 Planning Target Volume (PTV)

• In practice, it is often the result of a compromise between

two contradictory issues: making sure that the CTV
will receive the prescribed dose while at the same time
ensuring that OARs will not receive an excessive dose.

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 Planning Target Volume (PTV)
• Contains a CTV and a margin to account for
variation is size, shape and position relative
to treatment beams
PTV

Part VIII.3.7 Operational Considerations – Planning of physical Slide 26

treatment
 2.3.4 Treated Volume (TV)
• The volume of tissue enclosed by an isodose
surface selected and specified by the clinician as
being appropriate to achieve the aim of
treatment.
• For example, this may be the volume
encompassed within the 95% isodose surface
(with 100% in the centre of the PTV) for a
curative treatment plan.
 2.3.4 Treated Volume (TV)
•The TV should not be significantly larger than the PTV.
The use of 3D treatment planning and shaping the
radiation fields to the shape of the PTV using conformal
radiation delivery techniques ensures that the TV
encloses the PTV with as narrow a margin as possible.
This ensures minimal irradiation of surrounding OARs
while coverage of the PTV is assured.
 Treated volume
Treated volume – Volume enclosed by an isodose
surface selected as appropriate to achieve purpose
of treatment
Treated Volume

Part VIII.3.7 Operational Considerations – Planning of physical Slide 29

treatment
 2.3.5 Irradiated Volume (Iv)

• The tissue volume receiving a radiation absorbed

dose that is considered significant in relation to
normal tissue tolerance.
• This concept is not often considered in practice
but may be useful when comparing one or more
competing treatment plans.
• Clearly, it would be preferable to accept the plan
with the smallest IV, all else being equal.
 Irradiated volume
Irradiated volume – The volume that receives a
dose that is significant in relation to normal
tissue tolerance
Irradiated Volume

Part VIII.3.7 Operational Considerations – Planning of physical Slide 31

treatment
 2.3.6 Organs At Risk (Oar)
• Organs adjacent to the PTV which are non-target; do
not contain malignant cells
• The aim should therefore be to minimise irradiation of
OARs as they are often relatively sensitive to the effects
of ionising radiation and, if damaged, may lead to
substantial morbidity.
• The OARs to be considered will vary greatly according
to the anatomical region being treated, the size of the
PTV and the location of the PTV in these regions.
 2.3.6 Organs At Risk (Oar)

• The following are examples of the most common OARs that must be
considered:
1. Brain: lens of eye, optic chiasm, brain stem
2. Head & neck: lens of eye, parotid glands
3. Thorax: spinal cord, lungs
4. Abdomen: spinal cord, large bowel, small bowel, kidneys
5. Pelvis: bladder, rectum, femoral heads, large bowel, small bowel
 Organs at Risk (OAR)
• Normal tissues whose radiation
sensitivity could significantly influence
treatment planning and/or the dose
prescription

OARs
• Lung

• Spinal cord

Part VIII.3.7 Operational Considerations – Planning of physical Slide 34

treatment
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 2.4 Biological Factors (5 Rs)
2.4.1 Repair
2.4.2 Repopulation
2.4.3 Reoxygenation
2.4.4 Redistribution
2.4.5 Radiosensitivity
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 2.4 Biological Factor (5 Rs)
Repair
• The biological factors that
influence the response of
Repopulation
normal and neoplastic
tissues to fractionated
Reoxygenation radiotherapy
Redistribution

Radiosensitivity
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 2.4.1 Repair

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 2.4.1 Repair
• All cells repair radiation damage
• Repair is very effective because DNA is damaged significantly
more due to ‘normal’ other influences (e.g. temperature,
chemicals) than due to radiation
• The half time for repair, tr, is of the order of minutes to hours
 2.5.1 Repair
• It is essential to allow normal tissues to repair all repairable
radiation damage prior to giving another fraction of radiation.
• This leads to a minimum interval between fractions of 6 hours
• Spinal cord seems to have a particularly slow repair - therefore,
breaks between fractions should be at least 8 hours if spinal
cord is irradiated.
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 2.4.2 Repopulation

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 2.4.2 Repopulation
• In both tumours and normal tissues, proliferation of surviving cells may
occur during the course of fractionated treatment.
• Furthermore, as cellular damage and cell death occur during the course of
the treatment, the tissue may respond with an increased rate of cell
proliferation.
• The effect of this cell proliferation during treatment, known as
repopulation or regeneration (increase the number of cells during the
course of the treatment and reduce the overall response to irradiation)
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 2.4.2 Repopulation
• This effect is most important in early-responding normal tissues (e.g.,
skin, gastrointestinal tract) or in tumours whose stem cells are capable of
rapid proliferation; it will be of little consequence in late-responding,
slowly proliferating tissues (e.g., kidney), which do not suffer much early
cell death and hence do not produce an early proliferative response to the
radiation treatment.
• Repopulation is likely to be more important toward the end of a course of
treatment, when sufficient damage has accumulated (and cell death
occurred) to induce a regenerative response.
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 2.4.2 Repopulation
• The repopulation time of tumour cells appears to vary during
radiotherapy - at the commencement it may be slow (e.g. due to
hypoxia), however a certain time after the first fraction of radiotherapy
(often termed the “kick-off time”, Tk) repopulation accelerates.

• Repopulation must be taken into account when protracting/prolong

radiation e.g. due to scheduled (or unscheduled) breaks such as
holidays.
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 2.4.3 Reoxygenation

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 2.4.3 Reoxygenation
• Oxygen is an important enhancement for radiation effects (“Oxygen
Enhancement Ratio” (OER)
• The tumor may be hypoxic (in particular in the center which may
not be well supplied with blood)
• One must allow the tumor to re-oxygenate, which typically happens
a couple of days after the first irradiation
 2.4.3 Reoxygenation

• The response of tumours to large single doses of radiation is dominated by the

presence of hypoxic cells within them, even if only a very small fraction of
the tumour stem cells are hypoxic.
• Immediately after a dose of radiation, the proportion of the surviving cells that
is hypoxic will be elevated. However, with time, some of the surviving
hypoxic cells may gain access to oxygen and hence become reoxygenated and
more sensitive to a subsequent radiation treatment.
• Reoxygenation can result in a substantial increase in the sensitivity of tumours
during fractionated treatment.

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 2.4.4 Redistribution

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 2.4.4 Redistribution
• Cells have different radiation sensitivities in different parts of
the cell cycle
• Highest radiation sensitivity is in early S and late G2/M phase of
the cell cycle
G2 M (mitosis)

G1

S (synthesis)

G1
• Variation in the radiosensitivity of cells in different phases of the cell cycle results
in the cells in the more resistant phases being more likely to survive a dose of
radiation.
• Two effects can make the cell population more sensitive to a subsequent dose of
radiation.
1. Some of the cells will be blocked in the G2 phase of the cycle, which is usually a
sensitive phase.
2. Some of the surviving cells will redistribute into more sensitive parts of the
cell cycle.
• Both effects will tend to make the whole population more sensitive to fractionated
treatment as compared with a single dose.
• .
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 2.4.4 Redistribution
•The distribution of cells in different phases of the cycle
is normally not something which can be influenced -
however, radiation itself introduces a block of cells in G2
phase which leads to a synchronization
•One must consider this when irradiating cells with
breaks of few hours.
 2.4.5 Radiosensitivity

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 2.4.5 Radiosensitivity
• For a given fractionation course (or for single-dose
irradiation), the haemopoietic system shows a greater
response than the kidney, even allowing for the different
timing of response.

• Similarly, some tumours are more radioresponsive than

others to a particular fractionation schedule, and this is
largely due to differences in radiosensitivity.
 2.4.5 Radiosensitivity
High RS Medium RS Low RS
Bone Marrow Skin Muscle
Spleen Liver Bones
Thymus Heart Nervous system
Lymphatic Lungs
nodes
Gonads
Eye lens
Lymphocytes
(exception to the RS laws)
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2.5 Biological Effect of Ionizing Radiation
2.5.1 Dose Response Curve
2.5.1.1 Deterministic
2.5.1.2 Stochastic Effect
2.5.1.3 Sigmoid Curve
2.5.1.4 Cell Survival Curve
2.5.2 LET
2.5.3 OER
2.5.4 RBE Dr. Nik Noor Ashikin Bt Nik Ab Razak 62
 2.5 Biological Effect of Ionizing Radiation

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 2.5 Biological Effect of Ionizing Radiation

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 2.5 Biological Effect of Ionizing Radiation

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 2.5 Biological Effect of Ionizing Radiation

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 2.5 Biological Effect of Ionizing Radiation

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 2.5 Biological Effect of Ionizing Radiation

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 2.5 Biological Effect of Ionizing Radiation

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 Biological effects of radiation
in time perspective
Time scale Effects

Fractions of seconds Energy absorption

Changes in biomolecules
Seconds (DNA, membranes)

Biological repair

Minutes Change of information in cell

Hours Mutations in a
Days Cell death
Weeks Germ cell Somatic cell
Months Organ Clinical
death changes
Leukaemia
Years or
Cancer
Decades Hereditary
effects
Module Medical IX. 70
Generations
 2.5 Biological Effect of Ionizing Radiation
2.5 Biological Effect of Ionizing Radiation

Dose to the tumor determines

probability of cure
What matters in the end is
the biological effect! Dose to normal structures determines
probability of side effects and
complications
Dose to patient, staff and visitors
determines risk of radiation
detriment to these groups
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 2.5 Biological Effect

Biological Effect

Stochastic Effects Deterministic Effects

(carcinogenic and genetic effects) (tissue reactions)
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 2.5.1 Dose Response Curve

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 2.5.1.3 Sigmoid Curve (non-threshold)
Line 1:
No level of
Stochastic
radiation can be Effect
considered safe.
Diagnostic
Imaging

DOSE
RESPONSE
Line 2:
CURVE
Threshold is Line 3:
assumed, response
expected at lower
Non linear
doses.
dose response
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(Radiotherapy)
 2.5.1.1 Deterministic Effect

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 2.5.1.1 Deterministic Effect
Due to cell killing
Severity of harm is
(high dose given
dose dependent
over short period)
Have a dose
threshold Specific to
particular tissues

erythema DETERMINISTIC
skin breakdown EFFECTS/ Acute effect/
short term effect/
cataracts (High Dose) early effect
death
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 2.5.1.1 Deterministic Effect

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 Acute radiation syndrome
(ARS)

 ARS is the most notable deterministic effect of ionizing radiation

 Signs and symptoms are not specific for radiation injury but
collectively highly characteristic of ARS
 Combination of symptoms appears in phases during hours to
weeks after exposure
- prodromal phase
- latent phase
- manifest illness
- recovery (or death)
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 2.5.1.2 Stochastic Effect

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 2.5.1.2 Stochastic Effect
Due to cell changes and
proliferation towards a No dose threshold -
malignant disease applicable also to very
small doses

Severity (example
cancer) independent of
the dose
Probability of effect
increases with dose

Eg:
STOCHASTIC
-cancer induction EFFECT
(Somatic effect)
(low dose) Late effect / Chronic
-hereditary effects
effect)
2.5.1.2 Stochastic Effect
2.5 Biological Effect
Phases of cancer induction
and manifestation
Norma l Ce lls

Initia tion Muta te d Ce lls

Elimia tion Re pa ra tion

Pre -c a nc e r

Promotion

Minima l Ca nc e r

Progre ssion
Clinic a l Ca nc e r

Spre a ding
 2.5.1.3 Sigmoid Curve (non-threshold)

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 2.5.1.3 Sigmoid Curve (non-threshold)
Practically all the cells are
dead

Repairing cell
structures is still
possible

No repairing: a low dose

means a great damage

dose Dose
 2.5.1.3 Sigmoid Curve (non-threshold)

LD 50/60
amount of radiation
that will cause 50% of
exposed individuals to
die within 60 days

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 2.5.1.4 Cell Survival Curve

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 2.5.1.4 Cell Survival Curve

Biological Effects At Cellular Level Cellular effects of ionizing radiation are

studied by cell survival curves

Possible mechanisms of cell death: n = targets

• Physical death

% survival cells (semi logarithmic)

• Functional death
• Death during interphase Dq
• Mitotic delay (threshold)

• Reproductive failure D0
(radiosensitivity)

Dose
 2.5.1.4 Cell Survival Curve
• Do = 37% dose slope
Loge n = Dq / D0
- Dose required to reduce the number of clonogenic cells to
37% of their former value
• Dq = Quasi threshold dose n = targets

% survival cells (semi logarithmic)

- Dose at which straight portion extrapolated backward cuts
the dose axis
• n = extrapolation number D q

(threshold)
- Extrapolating the straight portion of the survival curve
until it cuts the “surviving fraction” axis D 0

(radiosensitivity)

Dose

 Radiosensitive cells are characterized by curves with steep

slope D0 and/or small shoulder (low n)
 2.5.2 LET

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 2.5.2 LET

LET

the linear rate of energy

defining the quality absorption by absorbing
medium as charged particle
of an ionizing traverses the medium
radiation beam
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Photon

Proton

Helium

Carbon

Oxygen

Neon
The Spatial Distribution of Ionizing Events Varies with
the Type of Radiation and can be defined by LET

Separation of ion clusters in relation to LOW LET

size of biological target Radiation

gamma rays

deep therapy
X-rays

soft X-rays

alpha-particle

HIGH LET
4 nm Radiation
 excitation and ionization
• A dose of 1 Gy will give 2x103
ionization events in 10-10 g (the size
of a cell nucleus). This can be
achieved by:
– 1MeV electrons
 particle
•700 electrons which give 6
ionization events per m.
– 30 keV electrons
•140 electrons which give 30
ionization events per m.
excitation – 4 MeV protons
ionization •14 protons which give 300
ionization events per m.
-ray
• The biological effectiveness of
’-ray these different radiations vary!

WMcB2008

http://dmco.ucla.edu/McBride_Lab
 X- or -radiation is sparsely ionizing; most damage can be
repaired
4 nm

Repairable Sublethal Damage

2 nm

WMcB2008

http://dmco.ucla.edu/McBride_Lab
 It is hypothesized that the lethal
lesions are large double strand
4 nm breaks with Multiply Damaged
Sites (MDS) that can not be
repaired. They are more likely to
occur at the end of a track

Unrepairable Multiply Damaged Site

2 nm Single lethal hit
Also known as  - type killing WMcB2008

http://dmco.ucla.edu/McBride_Lab
 At high dose, intertrack
repairable Sublethal Damage may
Accumulate forming
unrepairable, lethal MDS

Also known as  - type killing

WMcB2008

http://dmco.ucla.edu/McBride_Lab
 2.5.2 LET

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 2.5.3 Oxygen Enhancement Ratio

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 2.5.3 Oxygen Enhancement Ratio
• Oxygen is a powerful oxidizing agent and therefore acts as a
radiosensitizer if it is present at the time of irradiation (within msecs).
1 • Its effects are measured as the oxygen enhancement ratio (O.E.R.)

• The presence or absence of molecular oxygen within a cell influences

the biological effect of ionizing radiation: the larger the cell oxygenation
above anoxia, the larger is the biological effect until saturation of the
2 effect of oxygen occurs, especially for low LET radiations

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 2.5.3 Oxygen Enhancement Ratio

• The effect is quite dramatic for low LET (sparsely ionizing) radiations,
while for high LET (densely ionizing) radiations it is much less
3 pronounced

• The ratio of doses without and with oxygen (hypoxic vs. well-
oxygenated cells) to produce the same biological effect is called the
oxygen enhancement ratio (OER).
4 • O.E.R. = D(anox)/D(ox)

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 2.5.3 Oxygen Enhancement Ratio

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 2.5.3 Oxygen Enhancement Ratio

• For densely ionizing radiation, such as low-energy α-particles,

5 the survival curve does not have an initial shoulder

• In this case, survival estimates made in the presence and

absence of oxygen fall along a common line; the OER is
6 unity – in other words, there is no oxygen effect

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 Oxygen Enhancement Ratio (OER)
Dose required to produce a specific biological effect in the absence of oxygen
= Dose required for the same effect in its presence

OER varies with level of effect but can be 2.5 - 3 fold

1) Culture Cells
4) irradiate under oxic or hypoxic conditions
5) Plate cells and
grow for about 12 days
0 Gy 2Gy 4Gy 6Gy .. . ..
. ..
2) Suspend Cells
6) Count colonies
( trysinization) 1.0

S.F.
hypoxic
oxic
3) Count cells in hemocytometer 0.1

Physical Dose = Biological Dose 0.01

0 2 4 6 8 10
Dose (Gy)
WMcB2008

http://dmco.ucla.edu/McBride_Lab
 Clinical Relevance of Hypoxia

The effects of hypoxia were first

discovered in 1909 by Schwarz who
showed that strapping a radium source on
the arm gave less of a skin reaction than
just placing it there. This was used to give
higher doses to deep seated tumors.
Giacca and Brown
Pimonizadole (oxygen mimetic)
staining colorectal carcinoma

• Hypoxic areas occur almost solely in tumors and are more

radioresistant than oxic areas.
• Hypoxia contributes to treatment failure
• Reoxygenation occurs between radiation dose fractions giving a
rationale for dose fractionation
• The oxygen effect is greater for low LET than high LET radiation
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2.5.4 Relative Biological Effectiveness (RBE)

22/3/2017 Dr. Nik Noor Ashikin Bt Nik Ab Razak 112

 2.5.4 RBE

• Equal doses of different LET radiation DO

1 NOT produce equal biological effects

•A term relating the ability of radiations with

different LETs to produce a specific biologic
2 response is relative biological effectiveness (RBE)
113
 2.5.4 RBE

• RBE is defined as the comparison of a dose of

some test radiation to the dose of 250 kV x-
3 rays that produces the same biologic response

•250 kV x-rays or 1.17/1.33 MeV 60Co as the

4 standard radiation

114
 2.5.4 RBE
RBE is end-point dependent

Fractionated doses of dense vs. sparse ionizing beam:

The RBE of high LET beam becomes larger when the fraction number is increasing.
 The ICRP 19912.5.4
standard
RBE values for
relative effectiveness
WR (also RBE or
Radiation Energy Q)
x-rays, gamma rays, electrons,
positrons, muons 1
neutrons < 10 keV 5
10 keV - 100 keV 10
100 keV - 2 MeV 20
2 MeV - 20 MeV 10
> 20 MeV 5
protons > 2 MeV 2
alpha particles, nuclear fission
products,
heavy nuclei 20

Weighting factors WR (also termed RBE or Q factor, to avoid confusion with tissue weighting factors Wf) used to
calculate equivalent dose according to ICRP report 92
 Tissue Type Matters

ACUTE RESPONDING TISSUES

(responses seen during standard therapy) 1
Gut
Skin Surviving
Fraction Acute Responding
Bone Marrow Tissues and
Mucosa .1 Many Tumors
LATE RESPONDING TISSUES
(responses seen after end of therapy) Late Responding
Brain Tissues
.01
Spinal Cord 0 4 8 12 16 20
Kidney
Dose (Gy)
Lung
Bladder
Physical Dose = Biological Dose
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 2.5.4 RBE

Example
• To achieve 50% survival fraction, 250 kV x-ray needs 2
Gy, but the tested particle needs 0.66 Gy only

RBE = D250/Dt 2 = 2 / 0.66 = 3

RBE at survival fraction of 0.5 for the tested particle is 3.
2.5.4 RBE
 Questions on
Interaction of Radiation with Biological Matter:
what is biological dose?

Bill McBride
Dept. Radiation Oncology
David Geffen School Medicine
UCLA, Los Angeles, Ca.
wmcbride@mednet.ucla.edu

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 1. The lifetime of radicals in target molecules is
about
– 10-3 secs
– 10-6 secs
– 10-9 secs
– 10-12 secs

#2 – free radicals are highly unstable and reactive

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 2. Electromagnetic radiation is considered ionizing
if it has a photon energy greater than
– 1.24 eV
– 12.4 eV
– 124 eV
– 1.24 keV

#3 – this is sufficient to break bonds in biological

molecules

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3. The S.I. unit of absorbed dose is
– Becquerel
– Sievert
– Gray
– Roentgen

#3 The International System (IS) unit is the Gray, named

after the radiobiologist Louis “Hal” Gray who was based
in London
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 4. Which of the following are not charged
particles?
– Electrons
– Neutrons
– Protons
– Heavy ions
– Alpha particles

#2 – which is why they are called NEUTRons

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 5. Which of the following is NOT a characteristic of the
indirect action of ionizing radiation
– Production of diffusible free radicals
– Production of reactive oxygen species
– Involvement of anti-oxidant defenses
– Causes a change in redox within a cell favoring
reduction of constituents

#4 the free radicals produced makes ionizing

radiation an oxidative stress overall

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 6. Which of the following is true about the oxygen
enhancement ratio
– Is the same at all levels of cell survival
– Can be measured by the dog-leg in a cell survival
curve after single high dose irradiation of tumors
– Is the ratio of doses needed for an isoeffect in the
absence to the presence of oxygen
– Is low for cells in S cell cycle phase compared to
cells in G2/M phase

#3 responses should be compared by the doses

needed for a particular isoeffect. The OER varies with
the level of effect eg survival
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 7. Which of the following is true about Linear Energy
Transfer
– It is a measure of the biological effectiveness of
ionizing radiation
– Shows an inverse correlation with the oxygen
enhancement ratio
– Is maximal at a relative biological effectiveness of
150 keV/micrometer
– Is measured in keV/micrometer

#4 LET is an average value imparted per unit path length.

Because the radiations vary in energy, the LET is not
biologically very useful
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 8. The Relative Biological Effectiveness of a
radiation is
– Assessed by the dose required for to
produce the same effect as 250kVp X-rays
– Is the ratio of the dose required of 250 kVp
X-rays to that of the test radiation for a given
isoeffect
– Is directly related to Linear Energy Transfer
– Is about 3 for alpha particle radiation
#2 - again, measured by isoeffective doses – classically
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 9. Which of the following radiobiological
phenomena occurring between dose
fractions has little or no effect on normal
tissue radiation responses?
– Repair
– Redistribution of cells in the cell cycle
– Repopulation
– Reoxygenation

#4 – Normal tissues are generally considered to be well

oxygenated

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