The document provides an overview of key concepts related to radiation biology, including types of radiation, linear energy transfer (LET), and relative biological effectiveness (RBE). It emphasizes the importance of oxygen in enhancing radiation effects on tumors and discusses the impacts of hypoxia on treatment outcomes. The document concludes with insights on how LET and oxygen effects relate to the biological effectiveness of different types of ionizing radiation.

1. BY DR.SOUMYADIP ROY
MODERATOR: DR.SHYAMA SUDHA
PREM
ADDITIONAL PROFESSOR
RADIATION ONCOLOGY JIPMER
LET RBE OER

2. OVERVIEW
 BASIC CONCEPTS
 LET
 RBE with their relationship in between
 OER and factors controlling them
 Summary

3. BASIC CONCEPTS
 Types of radiation:
 IONIZING: able to eject
electron from atom or
molecule ,example: x ray
, gamma ray etc
 NONIONIZING: not able
to eject electron from an
atom or molecule ,
example: microwave ,
infrared (heat) wave ,
visible light etc

4. Cont.
 Types of ionizing radiation:
1) ELECTROMAGNETIC: x ray , gamma ray
2) PARTICULATE: electrons , neutrons ,
protons , carbons etc
 Types of ionization :
1)DIRECT: where radiation directly damages
cellular structure
2)INDIRECT: where radiation causes
production of fast electrons which cause
further ionization and damage.

5. Cont.
•Types of radiation
action:
1)Direct action :
Radiation directly
hits the target to
cause damage
2)Indirect action :
production of free
radical which cause
damage.

6. Cont.
 Types of radiation
as per degree of
ionization:
1) dense: alpha
particle
2) intermediate :
neutron
3) sparse : x ray ,
gamma ray

7. LET
 Stands for linear energy transfer
 Definition:The LET of charged particles in
medium is the quotient of dE/dl , where dE is
average energy locally imparted to the
medium by a charged particle of specified
energy in traversing a distance of dl. (ICRU ,
1962)
 Unit : kiloelectron volt per micrometer

8. Cont.
 Methods to calculate
LET:

9. Cont.
 LET is an average quantity because at
microscopic level , deposition of energy per
unit length of tract varies over a wide range.
 For neutrons biologic properties correlate
better with energy average.
 With increasing LET biologic effectiveness of
a radiation increases upto a level there after it
decreases (discussed later).

10. Cont.
LET for one
particular type of
radiation
decreases as
energy increases
because with
increasing energy
ionization along
the track becomes
more sparse

11. RBE

13. GETTING CELL SURVIVAL CURVE
 A graph is plotted with
surviving fraction in
logarathmic scale in y
axis and dose of
radiation in x axis

14. RBE:
 Definition:The RBE of some test radiation ®
is defined by the ratio D250/Dr , where D250
and Dr are , respectively, the doses of x rays
and the test radiation required for equal
biologic effect. (National Bureau of Standards
, 1954).
 RBE is not constant for a particular type of
radiation and varies according to the end
point chosen.

15. Cont.
 RBE for single doses is
large initially and
diminishes gradually
as the dose is
increased because for
neutrons unlike x ray
the initial shoulder is
narrow and the curve
is steeper

16. Cont.
 For fractionated dose
both of the curves
have several
shoulders but the size
of the shoulders are
more for x ray as the
sublethal damage
repair is more and cell
killing is less So RBE
increases for
neutrons.

17. Cont.
RBE depends on
1. Radiation quality
2. Radiation dose
3. Fractionation
4. Dose rate
5. Biologic system or end point

18. Cont.
 RBE as a function of
LET: As LET increases
from 2 kev/um for xrays
to 150 kev/um for alpha
particles survival curve
becomes steeper and
shoulder disappears.
Large shoulder
indicates repair of more
SLD.

19. Cont.
 RBE increases rapidly
after 10 kev/um and
peaks at 100 kev/um.
After that increase in
LET causes decrease in
RBE. Curve 1,2,3
represents survival
fractions 0.8,0.1 and
0.01 respectively

20. Cont.
 Optimal LET is 100
kev/um because at this
LET the average
separation of
ionization events just
coincides with the
diameter of DNA (2
nm) and therefore has
highest probability of
causing DSB

21. OER AND OXYGEN EFFECTS

22. WHY OXYGEN IS IMPORTANT IN
ONCOLOGY
 Oxygen is important for cell killing effect of
radiation
 Hypoxia has been found to cause tumour
progression and metastsis
 Hypoxia is implicated not only in
radioresistance but also chemoresistance
 Bleomycin , 5FU, cisplatin , methotrexate are
less effective against hypoxic cells (Grau and
Overgaard ,1992).

23. TUMOUR CONTAINS HYPOXIC
CELLS
Survival curve for mouse
subcutaneous
lymphosarcoma has
two parts. For 1st D0 is
1.1 Gy and for 2nd it is
2.6 Gy , indicating that
after 9 Gy 2nd part of the
curve is due to hypoxic
proportion of cells (1% ).

26. TYPES OF HYPOXIA IN TUMOURS
1. Acute (Martin Brown ,1980s):Due to
malformed vasculature which
periodically open and close.
1. Chronic (Thomilson and Gray ,1955): Due
to rapid rate of metabolism by tumour
cells oxygen is rapidly used up by initial
layer of cells of 100-180 micron thickness
surrounding capillaries.

27. OER
 It is the ratio of doses of radiation under
hypoxic to aerated condition needed to produce
same biologic effect.
Oxygen ‘fixes’ the damage produce by indirect
action of ionizing radiation.
 Value: 2.5-3.5 for sparsely ionizing
radiation(X ray , gamma ray) ,1.6 for
intermediate ionizing (neutron) , 1 for densely
ionizing radiation ( alpha particle)

28. Cont.
Radiation with high
LET has more direct
action of DNA
damage and
indirect action
decreases and so
also the
requirement of O2.

29. NATURE OF
OXYGEN EFFECT
OER for
asynchronously
dividing cells (where
most of the cells are in
G1 phase) is less in low
dose region than high
dose as because G1
phase is more
radiosensitive than S
phase

30. For particulate
radiations as the
direct ionizing
action is more so
effect of oxygen
becomes less (so is
OER)

31. THE TIME AND MECHANISM OF OXYGEN
ACTION
Within microseconds after
radiation exposure oxygen is
needed to be present

32. THE REQUIRED CONC. OF OXYGEN
 Very less as compared
to fully aerated
condition.
Radiosensitivity
becomes double 0.5 %
conc. Of O2 as
compared to absolute
hypoxia and further
increase in
radiosensitivity after 5%
O2 does not occur.

33. Cont.
 OER as a function of
LET:As the LET
increases the OER
decreases slowly at
first until LET reaches
60 kev/um when fall in
OER is rapid and at
LET of 200 kev/um
OER reaches 1.

34. Cont.
 Around LET of 100
kev/um there is
drastic rise in
biologic
effectiveness and
at the same time
OER decreases
(i.e., requirement
of oxygen
becomes less)

35. SUMMARY
 X ray and gamma rays are sparsely ionizing
radiation because the ionizations are well
separated in time and space
 Alpha particles and neutrons are densely
ionizing radiations
 LET is the energy transferred per unit length
of track.Typical values are 0.2 kev/um for
cobalt-60 gamma ray , 2kev/um for 250kv
xray , 166 kev/um for 2.5 Mev alpha particles

36. SUMMARY Cont.
 RBE for some test radiation (r) is the ratio
D250/Dr where D250 and Dr are doses of 250
kv X ray and the test radiation respectively to
produce equal biologic effect
 RBE depends on radiation quality (LET) ,
total dose , dose per fraction , dose rate ,
biologic system , end point
 OER is the ratio of doses in hypoxic to
aerated condition to produce same effect
 Small quantity of oxygen is needed for
radiosensitization.

37. Cont.
 Oxygen makes the free radical mediated
DNA damage permanent