Modeling ultra-high dose rate electron and proton FLASH effect with the physicochemical approach

Area of Science:

• Radiochemistry
• Radiation Biology
• Medical Physics

Background:

• The FLASH effect, a phenomenon in ultra-high dose rate (UHDR) radiotherapy, offers normal tissue sparing.
• A physicochemical model based on radiochemical kinetics was proposed to explain the FLASH effect.

Purpose of the Study:

• To extensively simulate and scrutinize the applicability of a physicochemical model for oxygen depletion and FLASH experiments.
• To investigate the model's performance with both proton and electron beams across various experimental parameters.

Main Methods:

• Numerical solution of coupled nonlinear ordinary differential equations governing radiochemical kinetics.
• Calculation of the area under the curve (AUC) for radical concentrations using dose and beam delivery parameters.
• Comparison of simulated AUC differences with experimental biological endpoints and oxygen depletion data.

Main Results:

• Modeled AUC differences correlated with the FLASH effect, showing reduced radical concentrations at UHDR.
• Simulations accurately predicted threshold dose rates for memory preservation in whole-brain irradiation.
• Linear correlations were found between radical AUC and biological endpoints (TGF-β1, leg contracture, IL-6) in proton FLASH experiments.

Conclusions:

• The physicochemical model effectively explains the FLASH effect by linking UHDR to reduced radical exposure.
• Normal tissue sparing in FLASH radiotherapy may be attributed to decreased peroxyl and superoxide radical concentrations.
• The model's findings align with experimental observations on oxygen depletion and differential effects on normal versus tumor tissues.