Zhang Qixian, Gerweck Leo E, Cascio Ethan, Gu Liqun, Yang Qingyuan, Dong Xinyue, Huang Peigen, Bertolet Alejandro, Nesteruk Konrad Pawel, Sung Wonmo, McNamara Aimee L, Schuemann Jan
Physics Division, Department of Radiation Oncology, Massachusetts General Hospital & Harvard Medical School, Boston, MA 02129, USA.
Cancers (Basel). 2023 Apr 13;15(8):2269. doi: 10.3390/cancers15082269.
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 mm 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.
据报道,超高剂量率照射比传统剂量率照射更能保护正常组织。这种组织保护作用被称为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效应原因的假说。由228 MeV质子笔形束提供一个剂量率约为120 Gy/s的16×12 mm椭圆形照射野。对C57BL/6j和免疫缺陷的Rag1/C57小鼠进行部分腹部照射。在照射后2天计数增殖的隐窝细胞,并在照射后280天测量肌层厚度。FLASH照射并未降低两种品系小鼠传统照射的发病率或死亡率;事实上,观察到FLASH照射小鼠的生存有变差的趋势。FLASH照射小鼠和传统剂量率照射小鼠之间的淋巴细胞数量没有显著差异。观察到FLASH照射和传统剂量率照射后增殖的隐窝细胞数量相似,肌层厚度也相似。120 Gy/s的部分腹部FLASH质子照射并未保护正常肠道组织,且未观察到淋巴细胞耗竭的差异。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的剂量率不会诱导FLASH效应,甚至可能导致更差的结果。