OER, LET and RBE

Presented By: Moderated By:

Vandana (JR-II) • Mr. Teerthraj
Dept. of Radiotherapy • Dr. Jitendra Verma
CSMMU, Lucknow
 Oxygen Enhancement Ratio (OER)

2 Presented by: Dr. Vandana, CSMMU, Lucknow 8/28/2011

 OER
• The oxygen enhancement ratio (OER) is the ratio of
doses under hypoxic to aerated conditions that
produce the same biologic effect.

• The presence or absence of molecular oxygen

dramatically influences the biologic effect of x-rays.

• Oxygen presence (aerated cells) increases radiation

effectiveness for cell killing.

• Lack of oxygen (hypoxic cells) results in more radio

resistant cells.
3 Presented by: Dr. Vandana, CSMMU, Lucknow 8/28/2011
Surviving Fraction
Nature of the Oxygen Effect

Cells are much more sensitive to x-rays in the presence of molecular oxygen than in
its absence (i.e., under hypoxia). The ratio of doses under hypoxic to aerated
conditions necessary to produce the same level of cell killing is called the oxygen
enhancement ratio (OER).

4 Presented by: Dr. Vandana, CSMMU, Lucknow 8/28/2011 4

 Oxygen Effect
 To produce its effect,
molecular oxygen must
be present during the
radiation exposure or
at least during the
lifetime of the free
radicals generated by
the radiation.

 Oxygen “fixes” (i.e.,

makes permanent) the
damage produced by
free radicals.
 In the absence of
oxygen, damage
produced by the
indirect action may be
repaired.

5 Presented by: Dr. Vandana, CSMMU, Lucknow 8/28/2011 5

 Oxygen Fixation
ion pairs
CH3 CH2•
free radicals
functional free radical,
group unpaired electron

Generally, the free-radical reactions go like this:

CH2• + O2 CH2O2
an organic peroxide “fixes” the indirect damage

(oxygen has no impact on direct damage)

6 Presented by: Dr. Vandana, CSMMU, Lucknow 8/28/2011 6

 Radio-sensitivity and O2 Concentration
 Most of the change of
sensitivity occurs as the
oxygen tension increases
from 0 to 30 mm Hg.

 A further increase of
oxygen content has little
further effect.

 A relative radio-sensitivity
halfway between anoxia
and full oxygenation
occurs for a pO2 of about 3
mm Hg, which
corresponds to a
Fig: The dependence of radio-sensitivity on oxygen concentration of about
concentration 0.5% oxygen.

7 8/28/2011 Presented by: Dr. Vandana, CSMMU, Lucknow 7

 OER Effect
 OER varies from 2-3,
increasing with dose

 Low-LET radiations
 oxygen effect is more
pronounced

 High-LET radiations
 oxygen effect is non-
existent (OER = 1)

Low-LET radiation

8 Presented by: Dr. Vandana, CSMMU, Lucknow 8/28/2011 8

 Other Radiations and the OER
15 MeV Neutrons particles

1.0 1.0
OER = 1.6 OER = 1.0

0.1 0.1

0.01 Hypoxic
0.01

0.001 Aerated 0.001

0 2 4 6 0 1.0 2.0 3.0

Dose, Gy Dose, Gy

High-LET radiation
9 Presented by: Dr. Vandana, CSMMU, Lucknow 8/28/2011 9
 Linear Energy Transfer (LET)

10 Presented by: Dr. Vandana, CSMMU, Lucknow 8/28/2011

 LET
 LET can be defined as “The energy deposited per unit track”

 Unit is KeV/ m

 The linear energy transfer (LET) of charged particles in the medium is

the quotient of dE/dx, where dE is the average energy locally imparted
to the medium by a charged particle in traversing a distance of dx.

11 Presented by: Dr. Vandana, CSMMU, Lucknow 8/28/2011

 On the following diagram, each dot
represents a unit of energy deposited. As
you see:
 Alpha particles impart a large amount of
energy in a short distance (densely
ionizing).
 Beta particles impart less energy than
dispersion of energy
alpha, but are more penetrating.
 Gamma rays impart energy sparsely and are
the most penetrating.air tissue
incident radiation

high LET ( , n, p)
greater radiotoxicity

low LET ( , x, ~ )
12 LET = linear energy transfer
 Typical LET values
Linear Energy
Radiation Transfer ( keV/µm )
Cobalt-60 γ-rays 0.2

250-kV x-rays 2.0

10-MeV protons 4.7

150-MeV proton 0.5

14-MeV neutrons Track Avg. 12 Energy Avg. 100

2.5-MeV α-particles 166

2-GeV Fe ions (space

1000
radiation )

13 Presented by: Dr. Vandana, CSMMU, Lucknow 8/28/2011

 The Optimal LET
 LET of about 100 keV/μm is
optimal in terms of producing a
biologic effect.

 At this density of ionization, the

average separation in ionizing events
is equal to the diameter of DNA
double helix which causes significant
Double Strand Breaks(DSBs). DSBs
are the basis of most biologic effects.

 The probability of causing DSBs is

low in sparsely ionizing radiation
such as x-rays that has a low RBE.

14 Presented by: Dr. Vandana, CSMMU, Lucknow 8/28/2011

 Effect of LET on cell survival

Fig: Survival curves for cultured cells of human origin exposed to 250-kV X-rays,15-MeV
neutrons, and 4-MeV alpha-particles. As the LET of the radiation increases, the survival curve
changes: the slope of the survival curves gets steeper and the size of the initial shoulder gets
smaller.
15
 OER and LET

Fig. :Oxygen enhancement ratio as a function of linear energy transfer.

 At low LET, corresponding to x- or γ-rays, the OER is between 2.5 and 3;

 As the LET increases, the OER falls slowly at first, until the LET exceeds about 60 keV/µm,
after which the OER falls rapidly and reaches unity by the time the LET has reached about 200
keV/µm

16 Presented by: Dr. Vandana, CSMMU, Lucknow 8/28/2011

 Relative Biologic Effectiveness (RBE)

17 Presented by: Dr. Vandana, CSMMU, Lucknow 8/28/2011

 RBE
In comparing different type of radiations, x-rays are used as the
standard. Relative Biologic Effectiveness (RBE) of radiation for producing
a given biological effect is given as below:

Dose in Gy from 250 KeV X-rays

RBE = Dose in Gy from another radiation source
to produce the same biologic response

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 RBE
 The amount or quantity of radiation is expressed in terms of the
absorbed dose, a physical quantity with the unit of Gray or Rad.
Absorbed dose is a measure of energy absorbed per unit mass of tissue.

 Equal doses of different types of radiation do not produce equal biologic

effects. One gray of neutrons produces a greater biologic effect than 1
gray of X-rays.

 The key to the difference lies in the pattern of energy deposition.

19 Presented by: Dr. Vandana, CSMMU, Lucknow 8/28/2011

 Factors that determine RBE

 Biologic system or
endpoint
 Dose level and the number
of fractions
 Dose Rate
 Radiation quality (LET)

20
 Biologic system or endpoint

 RBE varies according to the tissue

or endpoint studied.

 It has a marked influence on the

RBE values obtained.

 RBE values are high for tissues

that accumulate and repair a great
deal of Sub-Lethal Damage (SLD) and
low for those that do not repair SLD.

21
 RBE for different cells and tissues
Figure below illustrates the difference in intrinsic radiosensitivity among various types
of cells:
Fig: Survival curves for various
types of Clonogenic mammalian
cells irradiated with 300 kV X-rays
or 15-MeV neutrons.

 Variation in radiosensitivity
among different cell lines is
markedly less for neutrons than
for x-rays.

 Cells characterized by x-ray

survival curve with a large
shoulder, indicating that they
can accumulate and repair a large
amount of sub-lethal radiation
damage, show larger RBE for
neutrons.

 Conversely, cells for which x-

ray survival curve has little if any
shoulder exhibit smaller neutron
RBE values.
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 End Point
To measure the RBE of some test radiation, one first choose a biological system
in which the effect of radiations may be scored quantitatively as well as choose
an end point.

For Example: If We are measuring the RBE of fast neutrons compared with 250-
kV X-rays, using the lethality of plant seedlings as a test system, groups of plants
are exposed to a range of either X-rays or neutron doses.

 LD50 of X-rays (250-kV) in causing plant deaths is 6 Gy (600 rad)

 LD50 of neutrons in causing plant deaths is 4 Gy (400 rad)
 The RBE of neutrons compared with x-rays is then simply the ratio of 6:4
which is 1.5.

Note: LD50 is dose of radiation that result in death of half of the plants in a group.

23
 Figure: shows survival curves obtained if
mammalian cells in culture are exposed to
a range of doses of either fast neutrons or
250-kV X-rays.

For surviving fraction of .01,

RBE =(10 Gy dose of x-rays)/ (6.6 Gy dose
of neutrons) = 1.5

For surviving fraction of 0.6,

RBE =(3 Gy dose of x-rays)/ (1Gy dose of
neutrons) = 3.0

Because the X-rays and neutron

survival curves have different shapes, the
X-ray survival curve having an initial
shoulder and the neutron curve being an
exponential function of dose, the
resultant RBE depends on the level of
dose chosen.
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 Dose Level and fractionated doses
The RBE generally increases as the dose is decreased.
The RBE for a fractionated regimen with neutrons is greater than for a single
exposure, because a fractionated schedule consists of a number of small doses and
the RBE is large for small doses.
For a surviving fraction of 0.01 the RBE
for neutrons relative to X-rays is 2.6
(was 1.5 at single exposure). This is
direct consequence of larger shoulder
of x-ray curve.

The width of the shoulder represents a

part of the dose that is “wasted”; the
larger the number of fractions, the
greater the extent of the wastage.
Neutrons curve-almost no shoulder.

Net result is that neutrons become

progressively more efficient than x-rays
Fractionation of radiation dose increases cell as the dose per fraction is reduced and
survival the number of fraction is increased.
25
 RBE as a function of dose rate
The lower the dose
rate, the higher the
survival.

RBE can vary with the dose rate because the slope of the dose-response
curve for sparsely ionizing radiations, such as x- or γ-rays, varies critically
with a changing dose rate. In contrast, the biologic response to densely
ionizing radiations depends little on the rate at which the radiation is
26 delivered.
 RBE as a function of LET
 The LET at which the RBE reaches
a peak is much the same (about 100
keV/μm) for a wide range of
mammalian cells.

 As the LET increases, the RBE

increases slowly at first, and then
more rapidly as the LET increases
beyond 10 keV/ μm.

 Between 10 and 100 keV/ μm, the

RBE increases rapidly with increasing
LET and reaches the maximum at
about 100 keV μm.

 Beyond this value for the LET, the RBE again falls to lower values.

27
 In the case of sparsely ionizing X-rays the probability of a single track causing a
DSB is low, thus X-rays have a low RBE. At the other extreme, densely ionizing
radiations (ex. LET of 200 keV/ μm) readily produce DSB, but energy is “wasted”
because the ionizing events are too close together. Thus, RBE is lower than
optimal LET radiation.

28
 OER & RBE as a function of LET

Fig: Variation of OER and

RBE as a function of LET of
the radiation involved.

Variation of the OER and the RBE as a function of LET. The two curves are
virtually mirror image of each other. The optimal RBE and the rapid fall of OER
occur at about the same LET value, 100 keV/µm

29 Presented by: Dr. Vandana, CSMMU, Lucknow 8/28/2011

 Conclusion
• OER is the ratio of hypoxic-to-aerated doses

• OER decreases as LET increases

• Oxygen must be present during irradiation, or very soon

after (microseconds)

• Only a small of amount O2 is required (< 5%)

• LET – energy transferred per unit length of track

• Densely ionizing radiation – High LET, Sparsely ionizing

radiation – Low LET

30 Presented by: Dr. Vandana, CSMMU, Lucknow 8/28/2011

 • Optimal LET is 100 keV/μm

• OER reaches unity by an LET of about 200 kev/μm

• Relative biologic effectiveness (RBE) is the ratio D250/Dr

• For low LET radiation, RBE LET, for higher LET the
RBE increases to a maximum, the subsequent drop is
caused by the overkill effect.

• RBE is large for small doses.

• RBE values are higher for tissues that repair SLD.

31 Presented by: Dr. Vandana, CSMMU, Lucknow 8/28/2011

 Thank You

32 8/28/2011