Electron spin resonance measurements of radiation-induced radicals under conventional and ultra-high dose rate electron irradiation

Ultra-high dose rate (UHDR) radiotherapy has been shown in preclinical studies to reduce normal tissue toxicity without compromising tumour control, a phenomenon referred to as the Flash effect. The radiochemical and biological mechanisms responsible for this effect remain unclear. This study investigates radical formation and oxygen depletion under UHDR and conventional dose rate (CDR) conditions to gain mechanistic insight. Radical formation was investigated using electron spin resonance (ESR) spectroscopy with both spin trapping and spin probe techniques. Oxygen consumption was monitored continuously during irradiation to complement radical yield measurements. E3 medium containing either spin traps (DMPO, DEPMPO, BMPO) or spin probes (CMH, TMTH, CAT1H) was prepared under hypoxic, physioxic, and normoxic conditions. Irradiations were performed at the Electron Linac for beams with high Brilliance and low Emittance at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) with 30 MeV electrons across a broad range of dose rates (0.1 Gy s$^{−1}$–10$^5$ Gy s$^{−1}$). Spin probe measurements enabled consistent comparisons between CDR and UHDR, revealing a significant dependence of spin concentration on both oxygenation and dose rate. ... mehrIn contrast, spin trapping showed reduced radical yields with decreasing oxygen levels, but no significant dose-rate dependence. Direct comparisons between UHDR and CDR were limited by differences in the decay kinetics of the spin adducts. Oxygen measurements confirmed a reduced oxygen consumption at UHDR, with the extent of depletion strongly dependent on initial oxygen concentration. The results support the hypothesis that UHDR conditions promote radical–radical recombination, shifting the reaction equilibrium and reducing the pool of radicals available to react in the homogeneous chemical phase, particularly with oxygen. The combined application of ESR spin trapping, spin probes, and real-time oxygen measurements offers complementary insight into dose-rate-dependent radical processes.