Radical recombination and antioxidants: a hypothesis on the FLASH effect mechanism

Abstract

Purpose

FLASH (ultra-high dose rate) radiotherapy spares normal tissue while keeping tumor control. However, the mechanism of the FLASH effect remains unclear and may have consequences beyond the irradiated area.

Materials and methods

We reanalyze the available results of ultra-high-dose-rate-related experiments to find out the key points of the mechanism of the FLASH effect. Then, we present a hypothesis on the mechanism of the FLASH effect: FLASH beams generate a high transient concentration of peroxyl radicals leading to a high fraction of radical recombination, which results in less oxidation damage to normal tissue. For the cells containing higher concentrations of antioxidants, the fractions of radical recombination are smaller because the antioxidants compete to react with peroxyl radicals. Therefore the damages by different dose rate beams differ slightly in this condition. Since some tumors contain a higher level of antioxidants, this may be the reason for the loss of the protective effect in tumors irradiated by FLASH beams. The high concentration of antioxidants in tumors results in slight radiolytic oxygen consumption, and consequently the protective effect observed in in vitro experiment cannot be observed in in vivo experiment. To quantitatively elaborate our hypothesis, a kinetic model is implemented to simulate the reactions induced by irradiation. Two parameters are defined to abstractly study the factors affecting the reaction, such as dose rate, antioxidants, total dose and reaction rate constants.

Results and conclusions

We find that the explanation of the difference between in vivo and in vitro experiments is crucial to understanding the mechanism of the FLASH effect. Our hypothesis agrees with the results of related experiments. Based on the kinetic model, the effects of these factors on the FLASH effect are quantitatively investigated.

Keywords:

• Peroxyl radical
• antioxidant
• radical recombination
• radiation
• FLASH radiotherapy

Acknowledgments

The authors would like to thank Mr. Alexander Baikalov from Helmholtz Zentrum München for the linguistic proofreading of the manuscript.

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [Grant No. 12175114, 11875036 and U2167209] and Tsinghua University Initiative Scientific Research Program.

Notes on contributors

Ankang Hu

Ankang Hu is a PhD student at Department of Engineering Physics, Tsinghua University, Beijing, China.

Rui Qiu

Rui Qiu, Dr, is an Associate Professor at Department of Engineering Physics, Tsinghua University, Beijing, China.

Wei Bo Li

Wei Bo Li, Dr, is the Head of Research Group Optimization of Radiation Applications in Medicine, Institute of Radiation Medicine, Helmholtz Zentrum München German Research Center for Environmental Health (GmbH), Neuherberg, Germany.

Wanyi Zhou

Wanyi Zhou is a PhD student at Department of Engineering Physics, Tsinghua University, Beijing, China.

Zhen Wu

Zhen Wu, Dr, is a Senior Engineer at Department of Engineering Physics, Tsinghua University, Beijing, China.

Hui Zhang

Hui Zhang is a Senior Engineer at Department of Engineering Physics, Tsinghua University, Beijing, China.

Junli Li

Junli Li, Dr, is a Professor and Director of Radiation Protection and Environmental Protection Laboratory at Department of Engineering Physics, Tsinghua University, Beijing, China.