Dose‑Rate–Dependent Modulation of Radiolytic Hydroxyl Radical (•OH) Yield In Water Under Electron and Proton Flash Irradiation
Abstract
Purpose
FLASH radiotherapy (FLASH‑RT) employs ultra‑high dose rates (UHDR) that preferentially spare normal tissues relative to conventional dose‑rate radiotherapy (CONV‑RT) while maintaining tumor control, this is known as the FLASH effect. A proposed mechanistic explanation includes distinct radical–radical interactions occurring at UHDRs. However, direct experimental evaluation of this hypothesis remains challenging due to the need to quantitatively assess short‑lived radiolytic species. In this study, electron paramagnetic resonance (EPR) spectroscopy combined with spin trapping was used to quantify the dose‑rate dependence of hydroxyl radical (•OH) formation following electron and proton irradiations under UHDR and CONV dose‑rate conditions.
Methods
An experimental platform based on electron paramagnetic resonance (EPR) spectroscopy was developed using a Bruker Magnettech ESR5000 spectrometer and the spin trap 5,5‑dimethyl‑1‑pyrroline‑N‑oxide (DMPO). Samples consisting of DMPO solutions (0.01–10 mM) prepared in normoxic double‑distilled deionized water (100 µL) were loaded into 2‑mL glass tubes and irradiated using a modified Varian Clinac 16 MeV electron beam and a Hitachi synchrotron 80 MeV proton beam, both capable of delivering ultra‑high dose rates (UHDR). Dosimetry was performed using alanine pellets, Gafchromic film, and Monte Carlo (MC) simulations. Mean dose rates ranging from 0.01 to 250 Gy/s were employed. EPR measurements were conducted 120 s post‑irradiation, and the •DMPO‑OH spectral lines were integrated and compared against a calibration standard to quantify •DMPO‑OH concentrations and corresponding G‑values (•DMPO‑OH/Gy).
Results
UHDR irradiations exhibited higher G-values than CONV for both proton and electron beams. In the case of electron irradiations, a clear dose‑rate dependence was observed in the yield of •DMPO‑OH. Specifically, the G‑value increased with increasing dose rate, as evidenced by intermediate dose‑rate conditions falling between the CONV and UHDR regimes.
Conclusion
These findings highlight dose‑rate–dependent changes in hydroxyl radical formation under ultra‑high dose rate irradiation, shedding light on radiation chemical processes that may underlie the FLASH effect.