Proton FLASH: Impact of Dose Rate and Split Dose on Acute Skin Toxicity in a Murine Model

作者：Brita Singers Sørensen, Eleni Kanouta, C. Ankjærgaard, Line Kristensen, Jacob Johansen, Mateusz Sitarz, C.E. Andersen, Cai Grau, P.R. Poulsen · 发表于：International Journal of Radiation Oncology*Biology*Physics · 年份：2024 · DOI：10.1016/j.ijrobp.2024.04.071 · 被引用次数：88 · 研究领域：Radiation Therapy and Dosimetry、Advanced Radiotherapy Techniques、Effects of Radiation Exposure

PURPOSE: Preclinical studies have shown a preferential normal tissue sparing effect of FLASH radiation therapy with ultra-high dose rates. The aim of the present study was to use a murine model of acute skin toxicity to investigate the biologic effect of varying dose rates, time structure, and introducing pauses in the dose delivery. METHODS AND MATERIALS: The right hind limbs of nonanaesthetized mice were irradiated in the entrance plateau of a pencil beam scanning proton beam with 39.3 Gy. Experiment 1 was with varying field dose rates (0.7-80 Gy/s) without repainting, experiment 2 was with varying field dose rates (0.37-80 Gy/s) with repainting, and in experiment 3, the dose was split into 2, 3, 4, or 6 identical deliveries with 2-minute pauses. In total, 320 mice were included, with 6 to 25 mice per group. The endpoints were skin toxicity of different levels up to 25 days after irradiation. RESULTS: , which is the dose rate to induce a response in 50% of the animals, depended on the level of skin toxicity, with the higher toxicity levels displaying a FLASH effect at 0.7-2 Gy/s. Repainting resulted in higher toxicity for the same field dose rate. Splitting the dose into 2 deliveries reduced the FLASH effect, and for 3 or more deliveries, the FLASH effect was almost abolished for lower grades of toxicity. CONCLUSIONS: The dose rate that induced a FLASH effect varied for different skin toxicity levels, which are characterized by a differing degree of sensitivity to radiation...