300 Pasteur Dr, Grant S277, Stanford, CA 94305-5132, United States of America. Author to whom any correspondence should be addressed.
Phys Med Biol. 2019 Sep 11;64(18):185005. doi: 10.1088/1361-6560/ab3769.
Recent results from animal irradiation studies have demonstrated the potential of ultra-high dose rate irradiation (also known as FLASH) for reducing radiation toxicity in normal tissues. However, despite mounting evidence of a 'FLASH effect', a mechanism has yet to be elucidated. This article hypothesizes that the radioprotecting effect of FLASH irradiation could be due to the specific sparing of hypoxic stem cell niches, which have been identified in several organs including the bone marrow and the brain. To explore this hypothesis, a new computational model is presented that frames transient radiolytic oxygen depletion (ROD) during FLASH irradiation in terms of its effect on the oxygen enhancement ratio (OER). The model takes into consideration oxygen diffusion through the tissue, its consumption by metabolic cells, and its radiolytic depletion to estimate the relative decrease in radiosensitivity of cells receiving FLASH irradiation. Based on this model and the following parameters (oxygen diffusion constant [Formula: see text] = 2 · 10 cm s, oxygen metabolic rate m = 3 mmHg s, ROD rate L = [Formula: see text] mmHg Gy, prescribed dose D = 10 Gy, and capillary oxygen tension p = 40 mmHg), several predictions are made that could be tested in future experiments: (1) the FLASH effect should gradually disappear as the radiation pulse duration is increased from <1 s to 10 s; (2) dose should be deposited using the smallest number of radiation pulses to achieve the greatest FLASH effect; (3) a FLASH effect should only be observed in cells that are already hypoxic at the time of irradiation; and (4) changes in capillary oxygen tension (increase or decrease) should diminish the FLASH effect.
最近的动物辐照研究结果表明，超高剂量率辐照（也称为 FLASH）有可能降低正常组织的放射毒性。然而，尽管有越来越多的“FLASH 效应”证据，但尚未阐明其机制。本文假设 FLASH 辐照的放射保护作用可能是由于缺氧干细胞龛位的特异性保护，这在包括骨髓和大脑在内的几个器官中都有发现。为了探索这一假设，提出了一种新的计算模型，该模型根据其对氧增强比（OER）的影响来描述 FLASH 辐照期间瞬态放射分解氧耗竭（ROD）。该模型考虑了氧通过组织的扩散、代谢细胞对其的消耗以及其放射分解耗竭，以估计接受 FLASH 辐照的细胞相对放射敏感性的降低。基于该模型和以下参数（氧扩散常数 [Formula: see text] = 2 · 10 cm s，氧代谢率 m = 3 mmHg s，ROD 速率 L = [Formula: see text] mmHg Gy，规定剂量 D = 10 Gy，以及毛细血管氧张力 p = 40 mmHg），可以做出一些预测，这些预测可以在未来的实验中进行测试：（1）随着辐射脉冲持续时间从 <1 s 增加到 10 s，FLASH 效应应该逐渐消失；（2）应使用最少数量的辐射脉冲来沉积剂量，以实现最大的 FLASH 效应；（3）只有在照射时已经缺氧的细胞才会观察到 FLASH 效应；（4）毛细血管氧张力（增加或减少）的变化应该会减弱 FLASH 效应。
