Influencing Factors of the FLASH Effect: Unveiling the Importance of Free Radicals

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Hauptverfasser: Zhang, Yan, Huang, Chenyang, Hu, Ankang, Wang, Yucheng, Zhou, Wanyi, Qiu, Jiaqi, Wang, Jian, Fu, Qibin, Huang, Tuchen, Zha, Hao, Wang, Wei, Deng, Xiaowu, Li, Junli
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Veröffentlicht: 2024
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author Zhang, Yan
Huang, Chenyang
Hu, Ankang
Wang, Yucheng
Zhou, Wanyi
Qiu, Jiaqi
Wang, Jian
Fu, Qibin
Huang, Tuchen
Zha, Hao
Wang, Wei
Deng, Xiaowu
Li, Junli
author_facet Zhang, Yan
Huang, Chenyang
Hu, Ankang
Wang, Yucheng
Zhou, Wanyi
Qiu, Jiaqi
Wang, Jian
Fu, Qibin
Huang, Tuchen
Zha, Hao
Wang, Wei
Deng, Xiaowu
Li, Junli
contents Purpose: Our aim was to elucidate the critical factors responsible for inducing the FLASH effect, focusing on the role of free radicals through simulation and experimental approaches. Methods and Materials: The whole abdomen of C57BL/6 mice was irradiated with 6 MeV electron beam. The endpoint was acute intestinal toxicity quantified by histological score. Total doses ranging from 6 to 15 Gy were evaluated. The impact of the mean dose rate (MDR) was assessed in the range of 40 to 900 Gy/s. Dose per pulse (DPP) of 0.5 Gy and 3 Gy were compared. The recombination of peroxyl radicals were simulated. Further comparisons were conducted by incorporating the antioxidant amifostine. Results: When varying total doses with a constant MDR of 900 Gy/s, the FLASH effect was not observed until the dose reached 15 Gy. For a total dose of 15 Gy and varying MDR, the FLASH effect was observed only when MDR reached 100 Gy/s. For a dose of 15 Gy and an MDR of 150 Gy/s, no significant difference in biological effect was observed between low DPP and high DPP. The simulation results indicated that the fraction of peroxyl radicals recombination remained nearly zero at conventional dose rates. For FLASH irradiation, the recombination fraction increased linearly with the dose. Notably, the dose delivery time corresponding to 50% change in the recombination fraction was approximately 300 ms. The addition of amifostine effectively eliminated the difference between FLASH group and CONV group. Conclusions: The critical requirement for observing the sparing effect at the biological endpoint is the administration of an adequate dose within the time window of the radical reaction. Additionally, the important role of free radical was verified after introducing antioxidants, suggesting that the generation and recombination of free radicals are pivotal factors influencing the FLASH sparing effect.
format Preprint
id arxiv_https___arxiv_org_abs_2411_19194
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle Influencing Factors of the FLASH Effect: Unveiling the Importance of Free Radicals
Zhang, Yan
Huang, Chenyang
Hu, Ankang
Wang, Yucheng
Zhou, Wanyi
Qiu, Jiaqi
Wang, Jian
Fu, Qibin
Huang, Tuchen
Zha, Hao
Wang, Wei
Deng, Xiaowu
Li, Junli
Medical Physics
Purpose: Our aim was to elucidate the critical factors responsible for inducing the FLASH effect, focusing on the role of free radicals through simulation and experimental approaches. Methods and Materials: The whole abdomen of C57BL/6 mice was irradiated with 6 MeV electron beam. The endpoint was acute intestinal toxicity quantified by histological score. Total doses ranging from 6 to 15 Gy were evaluated. The impact of the mean dose rate (MDR) was assessed in the range of 40 to 900 Gy/s. Dose per pulse (DPP) of 0.5 Gy and 3 Gy were compared. The recombination of peroxyl radicals were simulated. Further comparisons were conducted by incorporating the antioxidant amifostine. Results: When varying total doses with a constant MDR of 900 Gy/s, the FLASH effect was not observed until the dose reached 15 Gy. For a total dose of 15 Gy and varying MDR, the FLASH effect was observed only when MDR reached 100 Gy/s. For a dose of 15 Gy and an MDR of 150 Gy/s, no significant difference in biological effect was observed between low DPP and high DPP. The simulation results indicated that the fraction of peroxyl radicals recombination remained nearly zero at conventional dose rates. For FLASH irradiation, the recombination fraction increased linearly with the dose. Notably, the dose delivery time corresponding to 50% change in the recombination fraction was approximately 300 ms. The addition of amifostine effectively eliminated the difference between FLASH group and CONV group. Conclusions: The critical requirement for observing the sparing effect at the biological endpoint is the administration of an adequate dose within the time window of the radical reaction. Additionally, the important role of free radical was verified after introducing antioxidants, suggesting that the generation and recombination of free radicals are pivotal factors influencing the FLASH sparing effect.
title Influencing Factors of the FLASH Effect: Unveiling the Importance of Free Radicals
topic Medical Physics
url https://arxiv.org/abs/2411.19194