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Linear Energy Transfer

By Dr. Deepa Gautam1st yr Resident, Radiotherapy

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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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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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Types of ionizing radiations

Electromagnetic radiationsParticulate radiations

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Electromagnetic radiations

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Particulate RadiationsElectrons 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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Particulate RadiationsNeutrons 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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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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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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Variation of ionization density associated with different types of radiation

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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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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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High LET RadiationsLow LET Radiations

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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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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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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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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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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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Factors Determining RBERadiation qualityRadiation doseNumber of dose fractionsDose rateBiologic system or end point

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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 x-ray curve indicates wastage of a part of dose each time in fractionated regime

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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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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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RBE AS A FUNCTION OF LET

As the LET increases, the RBEincreases 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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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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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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The Oxygen Effect and LETOxygen 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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Survival curves for cultured cells of human origin in hypoxic and aerated conditions determined for four different types of radiation.

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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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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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Thank You