Ultra-high dose-rate (FLASH) radiotherapy: Generation of early, transient, strongly acidic spikes in the irradiated tumor environment.

Monte Carlo simulations of γ/fast electron-radiolysis of water show that the in situ formation of HO temporarily renders each "native" isolated spur/track region very acidic. For pulsed (FLASH) irradiation with high dose rate, this early time, transient "acid-spike" response is shown to extend evenly across the entire irradiated volume. Since pH controls many cellular processes, this study highlights the need to consider these spikes of acidity in understanding the fundamental mechanisms underlying FLASH radiotherapy.