Purpose: Recent studies have suggested that 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 to quantitatively investigate 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 (LROD) during FLASH exposure. A mathematical model was applied for the analysis of oxygen tension (pO2) distribution in human tissues and the recovery of pO2 after FLASH irradiation. DNA damage and cell survival fractions after FLASH irradiation were calculated, and the impact of initial cellular pO2, FLASH pulse fractionation, pulse interval, and radiation quality of the source particles on ROD and the subsequent cellular responses were systematically evaluated.
Results: The simulated LROD range was 0.220–0.248 mmHg/Gy when pO2 ranged from 7.5–160 mmHg. The calculated DNA damage and cell survival fractions show that the radioprotective effect is more evident in cells with a lower pO2. Different irradiation setups alter the cellular responses by modifying the pO2. Single pulse delivery or multi-pulse delivery with pulse intervals lower than 10–50 ms resulted in fewer DNA damages and higher cell survival fractions. Source particles with a low radiation quality have a higher capacity to deplete oxygen, and thus, lead to a more conspicuous radioprotective effect.
Conclusion: Here, a systematic analysis of the cellular response following FLASH irradiation was performed to provided suggestions for future FLASH sparing effect study. 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 radiation quality are preferred for their conspicuous radioprotective effects.