Department of Engineering Physics, Tsinghua University, Beijing, China.
Key Laboratory of Particle & Radiation Imaging, Tsinghua University, Ministry of Education, Beijing, China.
Int J Radiat Biol. 2023;99(4):620-628. doi: 10.1080/09553002.2022.2110307. Epub 2022 Aug 10.
FLASH (ultra-high dose rate) radiotherapy spares normal tissue while keeping tumor control. However, the mechanism of the FLASH effect remains unclear and may have consequences beyond the irradiated area.
We reanalyze the available results of ultra-high-dose-rate-related experiments to find out the key points of the mechanism of the FLASH effect. Then, we present a hypothesis on the mechanism of the FLASH effect: FLASH beams generate a high transient concentration of peroxyl radicals leading to a high fraction of radical recombination, which results in less oxidation damage to normal tissue. For the cells containing higher concentrations of antioxidants, the fractions of radical recombination are smaller because the antioxidants compete to react with peroxyl radicals. Therefore the damages by different dose rate beams differ slightly in this condition. Since some tumors contain a higher level of antioxidants, this may be the reason for the loss of the protective effect in tumors irradiated by FLASH beams. The high concentration of antioxidants in tumors results in slight radiolytic oxygen consumption, and consequently the protective effect observed in in vitro experiment cannot be observed in in vivo experiment. To quantitatively elaborate our hypothesis, a kinetic model is implemented to simulate the reactions induced by irradiation. Two parameters are defined to abstractly study the factors affecting the reaction, such as dose rate, antioxidants, total dose and reaction rate constants.
We find that the explanation of the difference between in vivo and in vitro experiments is crucial to understanding the mechanism of the FLASH effect. Our hypothesis agrees with the results of related experiments. Based on the kinetic model, the effects of these factors on the FLASH effect are quantitatively investigated.
FLASH（超高剂量率）放疗在保持肿瘤控制的同时保护正常组织。然而，FLASH 效应的机制尚不清楚，其可能具有超出照射区域的后果。
我们重新分析了与超高剂量率相关的实验的现有结果，以找出 FLASH 效应机制的关键点。然后，我们提出了一个关于 FLASH 效应机制的假说：FLASH 射线产生高瞬态浓度的过氧自由基，导致自由基重组的分数较高，从而使正常组织的氧化损伤减少。对于含有较高浓度抗氧化剂的细胞，自由基重组的分数较小，因为抗氧化剂竞争与过氧自由基反应。因此，在这种情况下，不同剂量率射线的损伤略有不同。由于一些肿瘤含有较高水平的抗氧化剂，这可能是 FLASH 射线照射的肿瘤中保护作用丧失的原因。肿瘤中高浓度的抗氧化剂导致轻微的辐射分解氧消耗，因此在体内实验中观察不到体外实验中观察到的保护作用。为了定量阐述我们的假设，实施了一个动力学模型来模拟辐射诱导的反应。定义了两个参数来抽象地研究影响反应的因素，如剂量率、抗氧化剂、总剂量和反应速率常数。
我们发现，对体内和体外实验之间差异的解释对于理解 FLASH 效应的机制至关重要。我们的假设与相关实验结果一致。基于动力学模型，定量研究了这些因素对 FLASH 效应的影响。
