Absence of Tissue-Sparing Effects in Partial Proton FLASH Irradiation in Murine Intestine.
Absence of Tissue-Sparing Effects in Partial Proton FLASH Irradiation in Murine Intestine.
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超高剂量率辐照的正常组织保留效应（即FLASH效应）已被广泛报道。然而，我们的数据表明，并非所有剂量率高于40戈瑞/秒的辐照都能带来益处。我们发现腹部部分FLASH质子照射既不能提高生存率，也不能保存循环淋巴细胞。这些发现强调了了解诱发FLASH效应的条件的必要性，以获得成功的临床转化。据报道，超高剂量率辐射比常规剂量率辐射更能保护正常组织。这种组织保留被称为FLASH效应。我们研究了质子照射对肠道的FLASH效应，以及淋巴细胞耗竭是FLASH效应的一个原因的假设。228 MeV质子铅笔束提供了一个剂量率为~120 Gy/s的16 × 12 mm2椭圆场。对C57BL/6j和免疫缺陷小鼠Rag1−/−/C57进行部分腹部照射。照射后2天计数增殖的隐窝细胞，照射后280天测量外肌层厚度。FLASH辐照在两种小鼠中均未降低常规辐照的发病率或死亡率；事实上，在flash照射的小鼠中观察到更差的生存趋势。在FLASH和常规剂量率小鼠之间淋巴细胞数量无显著差异。在FLASH和常规剂量率照射后，观察到相似数量的增殖隐窝细胞和相似厚度的外肌层。120 Gy/s的腹部部分FLASH质子照射不影响正常肠道组织，淋巴细胞耗损无差异。这项研究表明，FLASH照射的效果可能取决于多种因素，在某些情况下，超过100 Gy/s的剂量率不会诱发FLASH效应，甚至可能导致更差的结果。
The normal tissue-sparing effect of ultra-high dose rate irradiation (i.e., FLASH effect) has been widely reported. However, our data suggest that not all irradiations with a dose rate above 40 Gy/s can confer benefits. We found that partial abdominal FLASH proton irradiation neither improved survival nor preserved circulating lymphocytes. These findings highlight the necessity to understand the conditions that induce the FLASH effect, for successful clinical translation. Ultra-high dose rate irradiation has been reported to protect normal tissues more than conventional dose rate irradiation. This tissue sparing has been termed the FLASH effect. We investigated the FLASH effect of proton irradiation on the intestine as well as the hypothesis that lymphocyte depletion is a cause of the FLASH effect. A 16 × 12 mm2 elliptical field with a dose rate of ~120 Gy/s was provided by a 228 MeV proton pencil beam. Partial abdominal irradiation was delivered to C57BL/6j and immunodeficient Rag1−/−/C57 mice. Proliferating crypt cells were counted at 2 days post exposure, and the thickness of the muscularis externa was measured at 280 days following irradiation. FLASH irradiation did not reduce the morbidity or mortality of conventional irradiation in either strain of mice; in fact, a tendency for worse survival in FLASH-irradiated mice was observed. There were no significant differences in lymphocyte numbers between FLASH and conventional-dose-rate mice. A similar number of proliferating crypt cells and a similar thickness of the muscularis externa following FLASH and conventional dose rate irradiation were observed. Partial abdominal FLASH proton irradiation at 120 Gy/s did not spare normal intestinal tissue, and no difference in lymphocyte depletion was observed. This study suggests that the effect of FLASH irradiation may depend on multiple factors, and in some cases dose rates of over 100 Gy/s do not induce a FLASH effect and can even result in worse outcomes.
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