Dependence of the radical dynamics on the beam temporal profile in FLASH radiotherapy

Abstract Objective. This study aims to investigate the impact of the beam temporal profile on the radical dynamics and inter-track interactions of FLASH radiotherapy, supporting parameter optimization for the equipment development, radio-biological experiments and clinical implementation. Approach. Monte–Carlo simulations based on the independent reaction time method were performed to analyze the dynamics after irradiation, including single-pulse or multi-pulses irradiation, pulse repetition rate, pulse width and dose. The physicochemical experiments were performed to measure the hydrated electron lifetimes for validation. The generation and recombination of hydroxyl radicals and hydrated electrons were recorded under 6 MeV electron irradiation with varying beam temporal profiles. The radial distributions of the radicals were statistically analyzed, and the inter-track interactions were assessed through a mathematical model. Main Results. The spatial distribution and temporal evolution of radicals were significantly affected by the beam temporal profiles. Compared with multi-pulses irradiation, single-pulse irradiation mode with a pulse width less than 1/10 of the radical lifetime, a repetition interval longer than the radical lifetime, and a dose exceeding 1 Gy/pulse can lead to rapid consumption of radicals within the first 30% of their lifetime, hence reduced the residual radical content. Instantaneous high dose rates induced overlapping of radical tracks. When the single-pulse dose exceeded 1 Gy, the overlap probability approached 100%, aligning with the dose threshold for the instantaneous radical combination. Significance. Under a low-duty cycle and high instantaneous dose-rate temporal profile, the radicals were rapidly consumed through track overlap, affecting FLASH effect. The optimized temporal profile can be used to guide the development of equipment and parameter settings in clinical practice to maximize the FLASH effect, such as the laser accelerators and superconducting photocathode guns.