Electron vs proton FLASH radiation on murine skin toxicity

Dose-response modification of FLASH has previously been established for acute skin toxicity in protons. This study used a similar experimental setup to quantify the dose-response modification of electron FLASH irradiation for acute skin- and late fibrotic toxicity in mice. The setup similarity enabled quantitative comparison of the acute skin response for electrons to protons. Female unanaesthetised C3D2F1 mice were restrained with the right hindleg fixated and submerged in a water bath for horizontal electron irradiation at 16 MeV. Mice were randomised in groups of varying single doses (19.4-57.6 Gy) and irradiated with either 0.162 Gy/s conventional (CONV) or 233 Gy/s FLASH dose rate using 8-10 mice per group. Acute skin toxicity was assessed daily from the 8th to the 28th day post-irradiation. The same mice were kept for a fibrotic assay of leg extension assessment done biweekly until 52 weeks post-irradiation. The dose-modifying factor (DMF) of FLASH was quantified from dose-response curves. Electron FLASH irradiated mice showed a considerable skin-sparing effect with a DMF of 1.45-1.54 and a smaller fibrotic-sparing effect with a DMF of 1.15. The development of acute skin toxicity was similar between CONV and FLASH groups with biological equivalent doses based on the DMF. The acute response of the electron irradiations was similar to previous reports on protons. Despite apparent differences, e.g. average and instantaneous dose rates, the acute skin toxicity of electron beams and previously published proton beams were remarkably similar regarding both biological response and quantified acute skin DMFs.