May oxygen depletion explain the FLASH effect? A chemical track structure analysis
May oxygen depletion explain the FLASH effect? A chemical track structure analysis
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DOI：
10.1016/j.radonc.2021.06.031
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发表时间：
2021-07-24
影响因子：
5.7
通讯作者：
Fuss, Martina C.
中科院分区：
文献类型：
--
作者：
Boscolo, Daria;Scifoni, Emanuele;Fuss, Martina C.
背景和目的：最近在动物模型中的观察显示，超高剂量率（“FLASH”）辐射治疗显著降低正常组织毒性，维持等效的肿瘤控制。这种“FLASH”效应对目标氧合的依赖性导致了氧“耗尽”可能是其主要驱动力的假设。Materials and Methods：在自下而上的方法中，从1 MeV电子在含氧水中的TRAX-CHEM Monte Carlo代码模拟的化学轨道演化开始，我们确定了短辐射脉冲后的氧消耗和辐解活性氧物种的产生。基于这些值，加权的有效剂量的氧增强比（OER）或在动态氧压下的体外细胞存活率计算和常规曝光相比，在恒定OER.Results：我们发现一个很好的协议，我们的Monte Carlo预测与实验值从含氧水中的辐解除氧。然而，本模型的应用程序公布的放射生物学实验条件表明，氧耗尽只能有一个微不足道的影响，通过氧增强辐射敏感性，特别是在典型的实验氧合的FLASH效应已经observed.Conclusion：我们表明，“氧耗尽”的假设的幅度和依赖性是不一致的，所观察到的生物效应的FLASH照射。虽然氧合在介导FLASH效应中起着重要作用，但我们得出结论，最先进的辐射化学模型不支持氧耗尽和辐射诱导的短暂缺氧作为主要机制。(C)2021作者（S）由爱思唯尔公司出版
Background and purpose: Recent observations in animal models show that ultra-high dose rate ("FLASH") radiation treatment significantly reduces normal tissue toxicity maintaining an equivalent tumor control. The dependence of this "FLASH" effect on target oxygenation has led to the assumption that oxygen "depletion" could be its major driving force.Materials and Methods: In a bottom-up approach starting from the chemical track evolution of 1 MeV electrons in oxygenated water simulated with the TRAX-CHEM Monte Carlo code, we determine the oxygen consumption and radiolytic reactive oxygen species production following a short radiation pulse. Based on these values, the effective dose weighted by oxygen enhancement ratio (OER) or the in vitro cell survival under dynamic oxygen pressure is calculated and compared to that of conventional exposures, at constant OER.Results: We find an excellent agreement of our Monte Carlo predictions with the experimental value for radiolytic oxygen removal from oxygenated water. However, the application of the present model to published radiobiological experiment conditions shows that oxygen depletion can only have a negligible impact on radiosensitivity through oxygen enhancement, especially at typical experimental oxygenations where a FLASH effect has been observed.Conclusion: We show that the magnitude and dependence of the "oxygen depletion" hypothesis are not consistent with the observed biological effects of FLASH irradiation. While oxygenation plays an undoubted role in mediating the FLASH effect, we conclude that state-of-the-art radiation chemistry models do not support oxygen depletion and radiation-induced transient hypoxia as the main mechanism. (C) 2021 The Author(s). Published by Elsevier B.V.