Luo Hui,Yang Chengliang,Paola Ballesteros-Zebadua,et al.Study on oxygen depletion and oxygen effect of FLASH irradiation[J].Chinese Journal of Radiological Medicine and Protection,2025,45(11):1115-1121
Study on oxygen depletion and oxygen effect of FLASH irradiation
Received:October 21, 2024  
DOI:10.3760/cma.j.cn112271-20241021-00406
KeyWords:FLASH irradiation  Oxygen depletion  Physioxia  Oxygen enhancement ratio  Oxygen effect
FundProject:河南省医学科技攻关计划项目(LHGJ20210171)
Author NameAffiliationE-mail
Luo Hui Department of Radiation Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China  
Yang Chengliang Department of Radiation Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China  
Paola Ballesteros-Zebadua Department of Radiation Oncology, Lausanne University Hospital, Lausanne 1002, Switzerland
Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suarez, Mexico City 52183, Mexico 
 
Javier Franco-Perez Department of Radiation Oncology, Lausanne University Hospital, Lausanne 1002, Switzerland
Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suarez, Mexico City 52183, Mexico 
 
Yuan Qigang School of Mathematics and Statistics, North China University of Water Resources and Electric Power, Zhengzhou 450046, China  
Ma Leijie Department of Radiation Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China  
Mao Ronghu Department of Radiation Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China  
Lei Hongchang Department of Radiation Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China  
Sun Yanan Department of Radiation Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China  
Song Shuai Department of Radiation Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China  
Ge Hong Department of Radiation Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China zlyygehong0199@zzu.edu.cn 
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Abstract::
      Objective To conduct a comparative analysis of the oxygen depletion and oxygen effect of FLASH irradiation and conventional irradiation by direct measurement of oxygen content. Methods The oxygen content in different tissues and organs of mice was measured using a phosphorescent probe. A subcutaneous xenograft tumor model in mice was established, to receive electron-beam irradiation at different doses and dose rates. The oxygen depletion of tumor and normal tissue was analyzed, and tumor control was evaluated. The oxygen depletion of conventional irradiation and FLASH irradiation was further analyzed using an in vitro model. The survival fraction (SF) of normal cells after conventional irradiation and FLASH irradiation was calculated using colony formation assay under different partial pressures of oxygen, and the data were fitted to the oxygen enhancement ratio (OER) curve. Results The mean oxygen content of subcutaneous xenograft tumor in mice was 1.28%, suggesting hypoxia. The mean oxygen content of normal tissue ranged from 3.51% to 6.53%, suggesting physioxia. In animal experiments, oxygen depletion was not observed during conventional irradiation. High-dose-rate (20 Gy/s) and ultra-high-dose-rate (FLASH, 40 Gy/s) irradiation produced oxygen depletion. During FLASH irradiation, with the increase of oxygen content, the oxygen depletion was 0.1-0.2 mm Hg/Gy for tumor tissue and 0.19-0.21 mm Hg/Gy for skin tissue, which tended to stabilize. FLASH irradiation maintained equivalent tumor control compared to conventional irradiation. The tumoricidal effect was significantly enhanced with the increase of oxygen content in the tissue (t=3.46, P<0.01). In in vitro experiments, the mean oxygen depletion rate was about 0.16 mm Hg/Gy for conventional irradiation and 0.16-0.18 mm Hg/Gy for FLASH irradiation, which did not change significantly with the increase of oxygen content. FLASH irradiation was associated with an oxygen effect. When the partial pressure of oxygen decreased from physioxia to hypoxia, the OER value significantly reduced. Conclusions Normal tissues and organs are in physioxia, which exhibits a lower oxygen content than that in the air. FLASH irradiation can consume a proportion of oxygen, producing an oxygen effect. When oxygen content decreases, the oxygen depletion rate slows down after FLASH irradiation.
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