Electron-Hole Liquid (EHL) Conjecture Rendering a Mechanism of Flash Radiotherapy
Abstract
Purpose
FLASH radiotherapy (FLASH-RT), utilizing ultra-high dose rates (UHDR), orders of magnitude above those of conventional RT, is unique by its significantly reduced damage to healthy tissues (sparing effect) that do not compromise the anti-tumor effectiveness. The underlying physics of FLASH RT remains yet to be understood with multiple studies reporting the absence of FLASH effect. Here we address the FLASH enigma theoretically, using basic physics with a goal of describing the FLASH RT criteria and kinetics.
Methods
We consider radiation-induced generation of charge carriers, followed by that of free radicals, such as the hydroxyl (•OH) known for their distractive actions, either useful (killing the tumor cells) or detrimental (killing the healthy cells). We utilized analytical modeling techniques based on the standard kinetic equations with the Coulomb interactions. High concentration of charge carriers under UHDR results in transition from electron-hole gas phase (typical of conventional RT) to electron-hole liquid (EHL), forming strong diffusion barriers leading to their mobility arrest and sparing effects.
Results
The diffusivity drops by many orders of magnitude between the phases of gas and liquid; hence, the charge carriers remain almost frozen and free radical generation suppressed in the EHL. That sparing mechanism is limited to the healthy tissues which are structurally organized enough to avoid the high-rate electron-hole recombination and maintain EHL. In the disordered tumor structure, the high-rate recombination decreases electron-hole concentration below that of EHL thus keeping the radical generation strong enough for antitumor effectiveness.
Conclusion
Introducing the concept of EHL for ultra-high dose rates, we derived the equations for time-dependent charge carrier concentration, yielding criteria for the minimum dose and dose rate simultaneously required for transition to EHL and thus FLASH condition. Our results demonstrate the binding effect of EHL, the temporal dynamic of reactive secondary species, and the sparing effect.