Work

Decoding the chemistry of the FLASH effect: a physicochemical model of dose-rate, pH and oxygen-dependent H₂O₂ production

Year: 2025

Type: article

Abstract: Objective. To elucidate the initial chemical mechanisms that may underlie the FLASH effect by developing and validating a unified simulation framework for the radiolysis of pure water. The goal is to create a single model capable of reconciling conflicting experimental and simulation data regarding H₂O₂ production and explaining key radiobiological observations across conventional (CDRs) and ultra-high dose rates (UHDRs) under varied oxygenation levels. Approach. An ordinary differential equation-based model was developed to simulate the homogeneous chemistry phase of water radiolysis. The framework incorporates a detailed chemical reaction network and a novel description of acid–base equilibrium, allowing pH to evolve dynamically. A key innovation is the integration of an empirically derived, dose-rate dependent G -value coefficient ( G F ( D R )) that anchors the simulation to experimental data. The temporal evolution of key species (H₂O₂, O₂, H₃O + , OH − ) is tracked to investigate the impact of dose rate and oxygen concentration. Main results. The model reproduces two key experimental findings relevant to the FLASH effect—previously challenging for simulations: decreased net H₂O₂ production at UHDR under physioxic conditions. This reduction (vs CDR) aligns with normal tissue sparing, while hypoxic (tumour-like) conditions show comparable H₂O₂ production at UHDR and CDR, consistent with iso-tumour control. These results confirm that H₂O₂ radiochemistry is profoundly influenced by both dose rate and oxygen levels. Significance. This work resolves a key discrepancy between previously published simulations and experimental data on UHDR water radiolysis. The model provides a robust, mechanistic foundation linking the physical parameter of dose rate to the distinct chemical environments that likely drive the differential biological outcomes of the FLASH effect. It serves as a powerful new tool for investigating the complex interplay between dose rate, oxygenation, and radiolytic chemistry.

Source: Physics in Medicine and Biology

DOI: 10.1088/1361-6560/ae1fcc

Authors: Romain Tonneau, Labarbe Rudi, Stéphane Lucas, Anne-Catherine Heuskin

Institutions: University of Namur, Namur Research Institute for Life Sciences, Ion Beam Applications (Belgium)

Language: English

Topic: Radiation Therapy and Dosimetry

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

Open Access status: hybrid

Estimated APC paid: $3,325

Funder: Service Public de Wallonie