Linear Energy Transfer[LET] Relative Biological Effectiveness[RBE] and Oxygen Enhancement Ratio Dr. Neeraj Suthar 1 st year resident Dept of Radiation oncology
The Deposition of Radiant Energy Radiation absorption of biologic material leads to ionization or excitation which is not random. But localized along the tracks of individual charged particle. Depends on the types of radiation involved.
Examples: -Photons of X-rays: Give rise to fast electrons Particle carrying unit charge Having very small mass -Neutrons: Give rise to recoil protons Particle carrying unit of charge Mass is 2000x of electrons -Alpha particle: Particle carrying 2 electric charge Mass is 4x of protons,8000x of electrons
Therefore spatial distribution of ionizing events produced by different particles varies -Radiation: 1. Sparsely ionizing:- Ionizing events are well separated in space. 2. Densely ionizing:- Produce dense column of ionization. -Energy decreases, density of ionization increases.
Linear Energy Transfer Definition :- Energy transfer per unit length of the track. ICRU Definition(1962):- The LET (L) of charged particles in medium is the quotient of dE /dl dE is the average energy locally imparted to the medium by a charged particle. dl is the distance. L= dE /dl Unit: keV /um LET is an average quantity because at microscopic level the energy per unit length of track varies over such a wide range.
The method of averaging makes little difference for X-rays or for Monoenergetic charged particles But the track avg. and energy avg. are different for neutrons. It is useful as a simple and naive way to indicate quality of different type of radiations. Energy increases, LET decreases,, biological effectiveness decreases
RELATIVE BIOLOGICAL EFFECTIVENESS [RBE] Amount or quantity of radiation is expressed as absorbed dose (unit- Gy ) ABSORBED DOSE- measure of energy absorbed per unit mass of tissue Equal doses of different types of radiation do not produce equal biological effects Eg.1Gy of neutrons produces a greater biologic effect than 1 Gy of X-rays.
The key to difference lies in the pattern of energy deposition at microscopic level. For comparison purpose, it is customary to use X-rays as the standard. Acc. to National Bureau of standards 1954- definition of RBE:- RBE of test radiation compared with X-ray is defined by D250/Dr where D250= dose of X-ray D r = dose of test radiation
RBE and FRACTIONATED doses Here we considered hypothetical treatment with neutrons consisting of 4 fractions- -at surviving fraction of 0.01, RBE for neutrons:- figure A(single dose) =1.5 figure B(fractionated dose)=2.6 This is a direct consequence of large shoulder that is characteristic of the X-ray curve, which must be repeated for each fraction. The width of shoulder represents a part of the doe that is “wasted”. Larger the number of fractions, the greater the extent of the wastage and hence RBE increment.
-The neutron survival curve has little or no shoulder, so there is correspondingly less wastage of dose from fractionation. -Conclusion :- “ neutrons become progressively more efficient than X-rays as the dose per fraction is reduced and the number of fractions is increased and for exposure to continuous low-dose-rate irradiation.
the neutron RBE is larger at a low dose rate than for acute exposure bcoz the effectiveness of neutrons decreases with dose rate to a much smaller extent that in case for X- or gamma rays, indeed, for low energy neutrons there is no loss of effectiveness. - In general, RBE values are HIGH for tissue that accumulate & repair a great deal of sub-lethal damage and LOW for those that do not .
RBE as a FUNCTION OF LET Illustrates the survival curves obtained for 250kVp X-rays, 15 MeV neutrons and 4 MeV alpha particles. As the LET increases from about 2 keV /um for X-rays upto 150 keV /um for alpha particles. - first the survival curve becomes steeper , - second, the shoulder of curve becomes progressively smaller as the LET increaes .
As the LET increases, the RBE Increases slowly at first and then more rapidly as the LET increases beyond 10 keV /um Between 10 -100 keV /um, the RBE increases rapidly incresing LET and reaches max. at 100keV/um. Beyond this value for the LET, the RBE again falls to lower values.
Optimal LET Most biological effective LET is that at which there is coincidence between diameter of DNA helix and average seprations of ionization
Factors that determine RBE Radiation quality (LET) Radiation dose Number of dose fractions Dose rate Biological system or end point
OXYGEN ENHANCEMENT RATIO [OER] Defined as- ratio of doses administered under hypoxic to areated conditions needed to achieve the same biological effect. Dose required under hypoxic condition OER = dose required under oxygenated condition to produce same biological effect
In the presence of oxygen ( areated cells), radiation effectiveness increases for cell killing i,.e . radiosensitive. In the absence of oxygen ( hypoxic cells), cells becomes radioresistent cells.
Mechanism of oxygen effect
THE OXYGEN EFFECT AND LET As the LET increases , the OER falls slowly at first, until the LET exceeds about 60kev/um After which the OER falls rapidly amd reaches up to 1 by the time LET has reached about 200 keV /um LET INVERSELY PROPORTIONAL TO OER for 250 kVp X-rays – 2.5 15 MeV neutrons -1.6 2.5 MeV alpha rays - 1
Summary X- and gamma rays are said to be sparsely ionizing because along the tracks of the electrons set in motion, primary ionizing events are well separated in space. Alpha particles and neutrons are densely ionizing because the tracks consist of dense colulmns of ionizing. LET is the energy transferred per unit length of track.
RBE of some test radiation(r) is : D250/Dr D250: dose of 250-kV x-rays Dr: dose of test radiation. - RBE increases with LET to a maximum at about 100keV/um, thereafter decreasing with higher LET. - For radiation with the optimal LET of 100keV/um , the average separation between ionizing events is similar to the diameter of the DNA double helix, so that DSBs can be most efficiently produced by a single track.