Linear Energy Transfer (LET) refers to the energy deposited by ionizing radiation per unit distance traveled through a material. High LET radiation like neutrons and alpha particles deposit energy densely along their tracks, while low LET radiation like x-rays and gamma rays deposit energy sparsely. High LET radiation is more destructive to biological tissue due to localized DNA damage. The relative biological effectiveness (RBE) of radiation, defined as the ratio of doses needed to produce an equal biological effect, increases with LET up to around 100 keV/μm, where DNA damage is maximized. The oxygen enhancement ratio, which quantifies radiation damage under hypoxic versus oxygenated conditions, decreases with increasing LET and reaches unity for LETs over 200 keV
2.
Ionization is the process of ejecting one or more
electrons from an atom and the radiation producing
such effect is known as ionizing radiation.
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3. Types of ionizing radiations
◦ Directly Ionizing: when absorbed in material, they
directly cause ionization leading to damage. Eg.
Electrons, α-particles, β-particles
◦ Indirectly ionizing: when absorbed in material,
they give up their energy to produce fast moving
charged particles which produce the damage. eg.
Electromagnetic radiation
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6. Particulate Radiations
Electrons are small, negatively charged particles
that can be accelerated to high speed close to that
of light by means of electrical device
Protons are positively charged particles and can
be accelerated to useful energies
α-particles are nuclei of helium atom consisting of
2 protons and 2 neutrons and emitted during the
decay of radionuclides like uranium, radium.
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7. Particulate Radiations
Neutrons are particles with mass similar to proton
but are chargeless and cannot be accelerated in an
electrical device.
They are produced if charged particle like
deuterium is accelerated to high energy and made
to hit on a suitable target.
They are also emitted as a by-product if
radioactive atoms undergo fission.
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8. Deposition of radiant energy
If radiation is absorbed in biologic material, the
events(ionization) tend to localize along the tracks
of individual particles in a pattern that depends upon
the type of radiation involved.
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9.
X-ray photons give rise to fast electrons carrying unit
electrical charge and have very less mass. The primary
events of x-rays are well separated in space and hence
said to be sparsely ionizing.
Cobalt 60-γ-rays are even more sparsely ionizing than
x-rays
Neutrons give rise to recoil protons carrying unit
electrical charge but mass 2000 times greater than that
of electrons. Neutrons are intermediately ionizing.
α-particles carry 2 electrical charges and 4 times
heavier than a proton. They are densely ionizing.
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11.
Linear energy transfer (LET) is the energy
transferred per unit length of the track.
Unit : kiloelectron volt per micrometer (keV/µm)of unit
density material.
The International Commission on Radiological
Units (1962) defined as:
◦ The linear energy transfer(L) of the charged particles in the
medium is the quotient of the dE/dl where dE is the average
energy locally imparted to the medium by a charged particle of
specified energy in traversing a distance of dl. That is L=dE/dl
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12.
LET can be only an average quantity because at the
microscopic level, the energy per unit length of track
varies over such a wide range that the average has
very little meaning.
This can be illustrated by the story of a Martian visitor
to Earth who arrives knowing that Earth is inhabited
by living creatures with an average mass of 1 g, may
encounter an elephant as the first creature.
An average has little meaning if individual variation is
great.
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15. High and Low LET Radiations
High LET Radiation:
◦ This is a type of ionizing radiation that deposit a large amount of
energy in a small distance.
◦ Eg. Neutrons , alpha particles
Low LET Radiation:
◦ This is a type of ionizing radiation that deposit less amount of
energy along the track or have infrequent or widely spaced
ionizing events.
◦ Eg. x-rays, gamma rays
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16. HIGH VS LOW LET RADIATIONS
•
High LET radiation ionizes water into H and OH radicals over a very short
track. In fig. two events occur in a single cell so as to form a pair of adjacent
OH radicals that recombine to form peroxide, H2O2, which can produce
oxidative damage in the cell.
•Low LET radiation also ionizes water molecules, but over a much longer
track. In fig. two events occur in separate cells, such that adjacent radicals
are of the opposite type: the H and OH radicals reunite and reform H2O.
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17. High vs Low LET Radiations
High-LET radiations are more destructive to biological material
than low-LET radiations.
The localized DNA damage caused by dense ionizations from
high-LET radiations is more difficult to repair than the diffuse DNA
damage caused by the sparse ionizations from low-LET
radiations.
High LET radiation results in lower cell survival per absorbed dose
than low LET radiation.
High LET radiation is aimed at efficiently killing tumor cells while
minimizing dose to normal tissues to prevent toxicity.
Biological effectiveness of high LET radiation is not affected by the
time or stage in the life cycle of cancer cells, as it is with low LET
radiation.
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19.
Track Average: calculated by dividing the track
into equal lengths and averaging the energy
deposited in each length.
Energy Average: calculated by dividing the track
into equal energy intervals and averaging the
lengths of the track that contain this amount of
energy.
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20. Relative Biologic
Effectiveness(RBE)
The National Bureau of Standards in 1954 defined
RBE as:
◦ The RBE of some test radiation(r) compared with x-rays is
defined by the ratio D250/Dr, where D250 and Dr are,
respectively, the doses of x-rays and the test radiation required
for the equal biologic effects.
Eg. A comparison of neutrons with 250kV x-rays in
lethality of plant seedlings. The end point of
observation being death of half of plants(LD50).
Suppose if LD50 for x-rays is 6Gy and for neutrons is
4Gy then RBE of neutrons compared with x-rays is 6:4
or 1.5
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22. SURVIVAL CURVES FOR MAMMALIAN CELLS
EXPOSED TO X-RAYS AND FAST NEUTRONS
•X-ray
survival curve has large
initial shoulder and neutron curve
has smaller shoulder and steeper
final slope
•RBE increases with decrease in
dose
•RBE for fractionated regimen with
neutrons is greater than for single
exposure.
•The little or no shoulder of neutron
curve indicates less wastage of
dose whereas wide shoulder of xray curve indicates wastage of a
part of dose each time in
fractionated regime
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23. RBE FOR DIFFERENT CELLS AND
TISSUES
The intrinsic radiosensitivity
among the various types of
cells differ from each other.
The curves demonstrate the
variation of radiosensitivites
for x-rays and markedly less
variation for neutrons.
X-ray survival curves have
large and variable initial
shoulder whereas for
neutrons ,it is small and less
variable
Hence RBE is also different
for different cell lines.
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24. RBE AS A FUNCTION OF
LET
•As
the LET increases from about
2keV/µm for x-rays upto 150
keV/µm for α-particles, the survival
curve becomes steeper and the
shoulder of the curve becomes
progressively smaller.
•Larger shoulder indicates the
accumulation and repair of the
large amount of sub-lethal radiation
damage
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25. RBE AS A FUNCTION OF LET
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 in fact reaches a
maximum at about 100 keV/µm.
Beyond this value for the LET, the
RBE again falls to lower values.
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26. The Optimal LET
LET of about 100keV/µm is optimal in terms of
producing biologic effect
At this density of ionization the average separation
between the ionizing events just about coincides with
the diameter of DNA double helix(2nm) and has highest
probability of causing DSBs by passage of a single
charged particle.
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27. In x-rays, probability of a single track causing a DSB is low
and requires more than one track.
Much more densely ionizing radiations (eg. LET of 200keV)
readily produce DBSs but energy is wasted as events
coincide with each other
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28. The Oxygen Effect and LET
Oxygen enhanced ratio(OER) is the ratio of
doses of radiation administered under hypoxic to
aerated conditions needed to achieve the same
biologic effect.
OER for different types of radiations are as follows:
◦
◦
◦
◦
X-rays: 2.5
Neutrons: 1.6
2.5-MeV particles:1
4-MeV particles: 1.3
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29. Survival curves for cultured cells of human origin in
hypoxic and aerated conditions determined for four
different types of radiation.
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30. OER AS A FUNCTION OF
LET
At low LET (x- or y-rays) with OER
between 2.5 and 3, as the LET
increases, the OER falls slowly
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
200keV/µm.
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31. OER AND RBE AS A FUNCTION OF LET
•The
rapid increase in RBE and the
rapid fall of OER occur at about the
same LET 100keV/µm .
•Two curves are virtually mirror
images of each other.
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