Room: AAPM ePoster Library
Purpose: Ultrahigh dose-rate radiotherapy with high pulse repetition rates (FLASH RT) demonstrates an incredible differential cell-killing effect that minimizes normal tissue toxicity. However, the effect is hardly observed from either in vivo or in vitro experiments, when the ultra-high dose-rate radiation has low pulse repetition rates. In this study, we performed a theoretical analysis based on radiation-induced oxygen depletion to explain the low pulse repetition rate situation.
Methods: In a cell irradiation study, radiolysis and oxygen diffusion together will determine the intracellular oxygen level ([O2]). By analyzing the effect of [O2] on cell survival fraction (SF) through the oxygen enhancement ratio (OER), we can compute SF after each pulse independently. The final SF is the product of SFs from the repeated pulses.
Results: For pulsed radiation sources with low repetition rates, [O2] is very close to a periodic function of time with the same repetition rate of the pulsed radiation source. The effective overall OER for the irradiation of cells will be the same as that with each pulse segment. Assuming the time function of [O2] after each pulse has a sigmoid shape with a very narrow transition width in time, the reduction in OER caused by radiation-induced oxygen depletion is proportional to the ratio between the characteristic diffusion-limited [O2] restoration time and the period of the pulsed radiation source. Therefore, at a low pulse repetition rate, the sparing effect of ultra-high dose-rate radiation on cells is predicted to be very limited.
Conclusion: We studied the impact of radiation-induced oxygen depletion on cell survival in ultra-short pulsed cell irradiation at low repetition rates. Our results may explain the observations that some ultra-short pulsed cell irradiation did not demonstrate FLASH RT effect, and offer insight on enhancing the effect. Further studies are needed to systematically validate our results.