LET, Linear Energy Transfer, Relative Biologic Effectiveness, Oxygen enhancement ratio, Dr. Vandana, KGMU, CSMMU, Lucknow, Radiation Oncology, Radiotherapy

1. OER, LET and RBE Presented By: Dr. Vandana Dept. of Radiotherapy CSMMU, Lucknow

2. Oxygen Enhancement Ratio (OER) 09/13/11 Presented by: Dr. Vandana, CSMMU, Lucknow

4. Nature of the Oxygen Effect 09/13/11 Presented by: Dr. Vandana, CSMMU, Lucknow Surviving Fraction 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).

6. Oxygen Fixation 09/13/11 Presented by: Dr. Vandana, CSMMU, Lucknow CH 3 functional group CH 2 • free radical, unpaired electron Generally, the free-radical reactions go like this: CH 2 • + O 2 CH 2 O 2  an organic peroxide “fixes” the indirect damage ion pairs free radicals (oxygen has no impact on direct damage)

10. Linear Energy Transfer (LET) 09/13/11 Presented by: Dr. Vandana, CSMMU, Lucknow

13. Typical LET values 09/13/11 Presented by: Dr. Vandana, CSMMU, Lucknow Radiation Linear Energy Transfer ( keV/ µ m ) 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 radiation ) 1000

15. 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.

17. Relative Biologic Effectiveness (RBE) 09/13/11 Presented by: Dr. Vandana, CSMMU, Lucknow

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

24. 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.

25. Dose Level and fractionated 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 as the dose per fraction is reduced and the number of fraction is increased. 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 . Fractionation of radiation dose increases cell survival

26. The lower the dose rate, the higher the survival. RBE as a function of dose rate 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 delivered.

28. 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.

32. 09/13/11 Thank You