| 罗辉,杨成梁,PaolaBallesteros-Zebadua,等.FLASH照射的氧消耗与氧效应研究[J].中华放射医学与防护杂志,2025,45(11):1115-1121.Luo Hui,Yang Chengliang,Paola Ballesteros-Zebadua,et al.Study on oxygen depletion and oxygen effect of FLASH irradiation[J].Chin J Radiol Med Prot,2025,45(11):1115-1121 |
| FLASH照射的氧消耗与氧效应研究 |
| Study on oxygen depletion and oxygen effect of FLASH irradiation |
| 投稿时间：2024-10-21 |
| DOI：10.3760/cma.j.cn112271-20241021-00406 |
| 中文关键词: FLASH照射 氧消耗 生理氧含量 氧增强比 氧效应 |
| 英文关键词:FLASH irradiation Oxygen depletion Physioxia Oxygen enhancement ratio Oxygen effect |
| 基金项目:河南省医学科技攻关计划项目(LHGJ20210171) |
| 作者 | 单位 | E-mail | | 罗辉 | 郑州大学附属肿瘤医院肿瘤放疗科, 郑州 450008 | | | 杨成梁 | 郑州大学附属肿瘤医院肿瘤放疗科, 郑州 450008 | | | PaolaBallesteros-Zebadua | 洛桑大学附属医院放疗科, 洛桑 瑞士 1002
墨西哥国家神经病学和神经外科研究所, 墨西哥 52183 | | | JavierFranco-Perez | 洛桑大学附属医院放疗科, 洛桑 瑞士 1002
墨西哥国家神经病学和神经外科研究所, 墨西哥 52183 | | | 袁期刚 | 华北水利水电大学数学与统计学院, 郑州 450046 | | | 马蕾杰 | 郑州大学附属肿瘤医院肿瘤放疗科, 郑州 450008 | | | 毛荣虎 | 郑州大学附属肿瘤医院肿瘤放疗科, 郑州 450008 | | | 雷宏昌 | 郑州大学附属肿瘤医院肿瘤放疗科, 郑州 450008 | | | 孙亚楠 | 郑州大学附属肿瘤医院肿瘤放疗科, 郑州 450008 | | | 宋帅 | 郑州大学附属肿瘤医院肿瘤放疗科, 郑州 450008 | | | 葛红 | 郑州大学附属肿瘤医院肿瘤放疗科, 郑州 450008 | zlyygehong0199@zzu.edu.cn |
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| 中文摘要: |
| 目的 通过直接检测氧含量法对比分析FLASH照射和常规照射的氧消耗与氧效应。方法 采用磷光探针检测小鼠不同组织和器官氧含量情况。构建小鼠皮下移植瘤模型, 实施不同剂量和剂量率电子线照射, 分析肿瘤和正常组织氧消耗, 观察肿瘤控制情况。采用体外模型分析常规照射和FLASH照射氧消耗水平。不同氧分压下, 应用克隆形成实验观察正常细胞常规照射和FLASH照射后存活分数(SF), 拟合氧增强比(OER)曲线。结果 小鼠皮下移植瘤平均氧含量为1.28%, 处于乏氧状态, 正常组织平均氧含量为3.51%~6.53%, 处于生理氧含量状态。动物实验中, 常规照射时未能观察到氧消耗;高剂量率(20 Gy/s)和超高剂量率(FLASH, 40 Gy/s)照射伴随氧消耗;FLASH照射时, 随着氧含量的增加, 肿瘤随组织氧消耗约为0.1~0.2 mm Hg/Gy, 而皮肤组织氧消耗为0.19~0.21 mm Hg/Gy, 趋于稳定水平。FLASH和常规照射肿瘤控制率相同, 随着组织氧含量升高, 肿瘤杀伤作用显著增强(t=3.46, P<0.01)。体外实验中, 常规照射氧消耗率约为0.16 mm Hg/Gy, FLASH照射氧消耗平均速率约为0.16~0.18 mm Hg/Gy, 随氧含量的增加变化不明显。FLASH照射存在氧效应, 当氧分压由生理氧含量转为乏氧时, OER值显著减小。结论 正常组织和器官处于生理氧含量状态, 低于空气氧含量。FLASH照射能够消耗部分氧, 存在氧效应;当氧含量降低时, FLASH照射后氧消耗速率下降。 |
| 英文摘要: |
| 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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