Modeling of cellular response after FLASH irradiation: a quantitative analysis based on the radiolytic oxygen depletion hypothesis

Hongyu Zhu; Junli Li; Xiaowu Deng; Rui Qiu; Zhen Wu; Hui Zhang

doi:10.1088/1361-6560/ac226d

Modeling of cellular response after FLASH irradiation: a quantitative analysis based on the radiolytic oxygen depletion hypothesis

Phys Med Biol. 2021 Sep 13;66(18). doi: 10.1088/1361-6560/ac226d.

Authors

Hongyu Zhu^{1

2

3}, Junli Li^{2

3}, Xiaowu Deng¹, Rui Qiu^{2

3}, Zhen Wu^{2

4}, Hui Zhang^{2

3}

Affiliations

¹ Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, People's Republic of China.
² Department of Engineering Physics, Tsinghua University, Beijing 100084, People's Republic of China.
³ Key Laboratory of Particle & Radiation Imaging (Tsinghua University), Ministry of Education, Beijing, People's Republic of China.
⁴ Nuctech Company Limited, Beijing 100084, People's Republic of China.

PMID: 34464946
DOI: 10.1088/1361-6560/ac226d

Abstract

Purpose.Recent studies suggest ultra-high dose rate (FLASH) irradiation can spare normal tissues from radiotoxicity, while efficiently controlling the tumor, and this is known as the 'FLASH effect'. This study performed theoretical analyses about the impact of radiolytic oxygen depletion (ROD) on the cellular responses after FLASH irradiation.Methods.Monte Carlo simulation was used to model the ROD process, determine the DNA damage, and calculate the amount of oxygen depleted (L_ROD) during FLASH exposure. A mathematical model was applied to analyze oxygen tension (pO₂) distribution in human tissues and the recovery of pO₂after FLASH irradiation. DNA damage and cell survival fractions (SFs) after FLASH irradiation were calculated. The impact of initial cellular pO₂, FLASH pulse number, pulse interval, and radiation quality of the source particles on ROD and subsequent cellular responses were systematically evaluated.Results.The simulated electronL_RODrange was 0.38-0.43μM Gy^-1when pO₂ranged from 7.5 to 160 mmHg. The calculated DNA damage and SFs show that the radioprotective effect is only evident in cells with a low pO₂. Different irradiation setups alter the cellular responses by modifying the pO₂. Single pulse delivery or multi-pulse delivery with pulse intervals shorter than 10-50 ms resulted in fewer DNA damages and higher SFs. Source particles with a low linear energy transfer (LET) have a higher capacity to deplete oxygen, and thus, lead to a more conspicuous radioprotective effect.Conclusions. A systematic analysis of the cellular response following FLASH irradiation was performed to provided suggestions for future FLASH applications. The FLASH radioprotective effect due to ROD may only be observed in cells with a low pO₂. Single pulse delivery or multi-pulse delivery with short pulse intervals are suggested for FLASH irradiation to avoid oxygen tension recovery during pulse intervals. Source particles with low LET are preferred for their conspicuous radioprotective effects.

Keywords: FLASH; Monte Carlo; cellular response; radiolytic oxygen depletion.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Computer Simulation
Humans
Linear Energy Transfer
Monte Carlo Method
Neoplasms*
Oxygen*

Substances

Oxygen