Ultrafast Tracking of Oxygen Dynamics during Proton FLASH

PURPOSE: Radiation therapy delivered at ultrafast dose rates, known as FLASH RT, has been shown to provide a therapeutic advantage compared to conventional radiotherapy by selectively protecting normal tissues. Radiochemical depletion of oxygen has been proposed to underpin the FLASH effect, however experimental validation of this hypotheses has been lacking, in part due to the inability to measure oxygenation at rates compatible with FLASH. METHODS AND MATERIALS: We present a new variant of the phosphorescence quenching method for tracking oxygen dynamics with rates reaching up to ~3.3 kHz. Using soluble Oxyphor probes we were able to resolve, both in vitro and in vivo, oxygen dynamics during the time of delivery of proton FLASH. RESULTS: (1) In vitro in solutions containing bovine serum albumin (BSA) the O(2) depletion g-values (moles/L of O(2) depleted per radiation dose, e.g. μM/Gy) are higher for conventional irradiation (by ~13% at 75 μM [O(2)]) than for FLASH, and in the low-oxygen region (