Dosimetry and chemical yield analysis of metal nanoparticles in FLASH radiotherapy: a Monte Carlo study

The integration of metallic nanoparticles into radiotherapy protocols has been recognized as a promising strategy for modulating dose deposition and enhancing therapeutic efficacy. In this study, the TOPAS Monte Carlo toolkit was employed to evaluate the radio-chemical effects of high-Z nanoparticles under both conventional and ultra-high dose rate (FLASH) irradiation conditions. Local energy deposition was found to increase in the presence of nanoparticles due to the emission of low-energy secondary electrons. However, the impact on chemical yields-particularly hydrogen peroxide (H 2 O 2 )-was observed to be nonlinear and strongly dependent on nanoparticle composition, beam modality, and dose rate. Under FLASH conditions, a significant reduction in H 2 O 2 yields was attributed to accelerated radical recombination and modified diffusion kinetics. Moreover, nanoparticle-mediated interactions introduced spatial heterogeneity in radical concentrations, potentially contributing to the simultaneous occurrence of tumor control and normal tissue sparing observed in FLASH radiotherapy. These findings emphasize the necessity of incorporating both physical and chemical mechanisms into nanoparticle-assisted FLASH treatment planning, and highlight the importance of future experimental validation to support simulation-based predictions.