Significant changes in yields of 7-hydroxy-coumarin-3-carboxylic acid produced under FLASH radiotherapy conditions

FLASH radiotherapy appears to kill off tumor cells while sparing healthy tissues, by irradiation at ultra high dose rate (>40 Gy s^-1). The present study aims to clarify the mechanism of the sparing effect by proton irradiation under the FLASH conditions from a viewpoint of radiation chemistry. To do so, we evaluate radiation chemical yields (G values) of 7-hydroxy-coumarin-3-carboxylic acid (7OH-C3CA), which is produced by water radiolysis using coumarin-3-carboxylic acid (C3CA) solution as a radical scavenger of hydroxyl radicals. We shoot 27.5 MeV protons in the dose rate ranging from 0.05 to 160 Gy s^-1. The recombination process of hydroxyl radicals produced is followed by varying the concentration of C3CA from 0.2 to 20 mM, which corresponds to the scavenging time scale from 7.1 to 714 ns. The G value of 7OH-C3CA produced decreases with increasing dose rate on the same scavenging time scale. Additionally, the trend of the relative G value normalized at a scavenging time scale of 100 ns, where radical-radical reaction subsides, is consistent in the examined dose rate range. This finding implies that G values of 7OH-C3CA produced reduce with increasing dose rate due to the oxygen depletion. We experimentally present that the sparing effect for healthy tissues would be seen even with a proton beam under the FLASH conditions due to the depletion of oxygen.