Radioprotective effect of X‐ray abdominal FLASH irradiation: Adaptation to oxidative damage and inflammatory response may be benefiting factors
Radioprotective effect of X‐ray abdominal FLASH irradiation: Adaptation to oxidative damage and inflammatory response may be benefiting factors
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X射线腹部FLASH照射的放射防护作用：对氧化损伤和炎症反应的适应可能是有益因素
DOI：
10.1002/mp.15680
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Xiaowu Deng
中科院分区：
文献类型：
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作者：
Hongyu Zhu;Dehuan Xie;Yiwei Yang;Shaomin Huang;Xingwang Gao;Yinglin Peng;Bin Wang;Jianxin Wang;Dexin Xiao;Dai Wu;Changzhi Li;Chenghua Li;Chao-Nan Qian;Xiaowu Deng
据报道，超高剂量率照射（FLASH-IR）在肿瘤控制中是有效的，同时降低正常组织的放射毒性。然而，这种现象的机制仍然不清楚。此外，临床放射治疗中最常用的高能X射线FLASH实验也鲜有报道。本研究旨在研究6 MV X射线FLASH-IR或常规剂量率IR（CONV-IR）的放射生物学响应。FLASH-IR使用成都太赫兹自由电子激光（CTFEL）装置的超导直线加速器，使用金刚石辐射探测器和CeBr 3闪烁探测器来监测FLASH脉冲的时间结构和剂量率。BALB/c裸鼠接受全腹6 MVX线FLASH-IR或CONV-IR照射，处方剂量为15戈伊或10戈伊，照射绝对剂量用EBT 3胶片监测。在IR后24小时对小鼠实施安乐死以评价急性组织反应或随访6周以观察晚期反应和存活概率。在FLASH-IR中，小鼠体中心平均剂量率>150戈伊/s，瞬时剂量率>5.5 × 105戈伊/s。在对接受15戈伊IR的小鼠进行6周随访后，FLASH组显示出比CONV组更快的体重恢复和更高的存活率。组织学分析表明，FLASH-IR组小鼠急性肠道损伤程度低于CONV-IR组;全血细胞计数和细胞因子浓度检测发现，FLASH-IR和CONV-IR组小鼠急性期炎性细胞计数和促炎细胞因子浓度均升高，而FLASH照射组小鼠晚期炎性细胞计数和促炎细胞因子浓度均显著降低。在急性期，FLASH组的活性氧（ROS）信号强度明显高于CONV组，脂质过氧化反应明显减轻。两组间炎症反应和氧化还原状态的差异可能是FLASH-IR后放射毒性降低的原因，ROS对FLASH-IR效应的影响有待进一步研究。
Ultrahigh dose-rate irradiation (FLASH-IR) was reported to be efficient in tumor control while reducing normal tissue radiotoxicity. However, the mechanism of such phenomenon is still unclear. Besides, the FLASH experiments using high energy X-ray, the most common modality in clinical radiotherapy, are rarely reported. This study aims to investigate the radiobiological response using 6 MV X-ray FLASH-IR or conventional dose-rate IR (CONV-IR).The superconducting linac of Chengdu THz Free Electron Laser (CTFEL) facility was used for FLASH-IR, a diamond radiation detector and a CeBr3 scintillation detector were used to monitor the time structure and dose rate of FLASH pulses. BALB/c nude mice received whole abdominal 6 MV X-ray FLASH-IR or CONV-IR, the prescribed dose was 15 Gy or 10 Gy and the delivered absolute dose was monitored with EBT3 films. The mice were either euthanized 24 h post-IR to evaluate acute tissue responses or followed up for 6 weeks to observe late-stage responses and survival probability. Complete blood count, histological analyses, and measurement of cytokine expression and redox status were performed.The mean dose rate of >150 Gy/s and instantaneous dose rate of >5.5 × 105 Gy/s was reached in FLASH-IR at the center of mice body. After 6 weeks' follow-up of mice that received 15 Gy IR, the FLASH group showed faster body weight recovery and higher survival probability than the CONV group. Histological analysis showed that FLASH-IR induced less acute intestinal damage than CONV-IR. Complete blood count and cytokine concentration measurement found that the inflammatory blood cell counts and pro-inflammatory cytokine concentrations were elevated at the acute stage after both FLASH-IR and CONV-IR. However, FLASH irradiated mice had significantly fewer inflammatory blood cells and diminished pro-inflammatory cytokine at the late stage. Moreover, higher reactive oxygen species (ROS) signal intensities but significantly reduced lipid peroxidation were found in the FLASH group than in the CONV group in the acute stage.The radioprotective effect of 6 MV X-ray FLASH-IR was observed. The differences in inflammatory responses and redox status between the two groups may be the factors responsible for reduced radiotoxicities following FLASH-IR. Further studies are required to thoroughly evaluate the impact of ROS on FLASH effect.