Work

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

Year: 2021

Type: article

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 (pO 2 ) distribution in human tissues and the recovery of pO 2 after FLASH irradiation. DNA damage and cell survival fractions (SFs) after FLASH irradiation were calculated. The impact of initial cellular pO 2 , FLASH pulse number, pulse interval, and radiation quality of the source particles on ROD and subsequent cellular responses were systematically evaluated. Results. The simulated electron L ROD range was 0.38–0.43 μ M Gy −1 when pO 2 ranged 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 pO 2 . Different irradiation setups alter the cellular responses by modifying the pO 2 . 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 pO 2 . 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.

Source: Physics in Medicine and Biology

DOI: 10.1088/1361-6560/ac226d

Authors: Hongyu Zhu, Junli Li, Xiaowu Deng, Rui Qiu, Zhen Wu, Hui Zhang

Institutions: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Tsinghua University, Nuctech (China)

Language: English

Topic: Radiation Therapy and Dosimetry

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Natural Science Foundation of China, National Key Research and Development Program of China