Quantifying the flash effect and its dependence on average dose rate in vivo for 6 MeV electron and 6 MV photon beams

Abstract

This study shows that an increase in average dose rate delays the onset, and reduces the severity, of radiation induced skin toxicity in mice following hemi-thorax irradiation. The FLASH sparing effect's magnitude and dependence on dose rate appear similar following irradiations using 6 MV photon and 6 MeV electron beams.

Fig. 1

Increasing the average dose rate of photon beam irradiations delays the radiotoxicity emergence and reduces skin toxicity. (A) Skin toxicity scoring scale with representative pictures. (B-D) Skin radiotoxicity emergence. Right lung of mice was irradiated with a single dose of (B) 20 Gy, (C) 25 Gy, or (D) 30 Gy at different dose rates and mice were monitored every other day to determine the time of skin toxicity onset. Mean values are shown with error bars representing ± SEM. (E-G) Macroscopic skin lesions scoring at 8 weeks post irradiation, based on the skin toxicity scoring scale, after (E) 20 Gy, (F) 25 Gy, or (G) 30 Gy photon beam irradiation. Bars represent the median and red dots indicate animals that had to be euthanised early for meeting skin toxicity euthanasia criteria (moist desquamation-ulceration). * p <0.05; ** p <0.01; *** p <0.001; **** p <0.0001. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Increasing the average dose rate of electron beam irradiations delays the radiotoxicity emergence and reduces skin toxicity. (A) Skin radiotoxicity emergence. Right lung of mice was irradiated with electrons with a single dose of 30 Gy at different dose rates and mice were monitored every other day to determine the time of skin toxicity onset. Mean values are shown with error bars representing ± SEM. (B) Kaplan-Meier survival curves for 30 Gy irradiation at different dose rates irradiation (n =5 for 1 Gy/s group, n =6 for 1,800 Gy/s group and n =7 for the other groups). (C) Macroscopic skin lesions scoring at 8 weeks post irradiation, based on the skin toxicity scoring scale, for 30 Gy irradiation at different dose rates. A separate experiment evaluating (D) skin radiotoxicity emergence and (E) macroscopic skin lesions scoring at 8 weeks post irradiation, for mice irradiated with electron beams in the dose range of 20 to 30 Gy in a single fraction at 0.1 Gy/s (left panel), 30 Gy/s (middle panel) or ≥1,800 Gy/s (right panel). Bars represent the median and red dots indicate animals that had to be euthanised early for meeting skin toxicity euthanasia criteria (moist desquamation-ulceration or moist desquamation that did not improve after 10 days). * p <0.05; ** p <0.01; *** p <0.001; **** p <0.0001. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)