Electron ultra-high dose rate FLASH irradiation study using a clinical linac: Linac modification, dosimetry, and radiobiological outcome
Electron ultra-high dose rate FLASH irradiation study using a clinical linac: Linac modification, dosimetry, and radiobiological outcome
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使用临床直线加速器的电子超高剂量率闪光照射研究：直线加速器修改、剂量测定和放射生物学结果
DOI：
10.1002/mp.15920
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发表时间：
2022-08-27
期刊：
影响因子：
3.8
通讯作者：
Qian，Chao-Nan
中科院分区：
文献类型：
--
作者：
Xie，De-Huan;Li，Yi-Chuan;Qian，Chao-Nan
研究目的超高剂量率闪光照射（FLASH‐IR）与常规照射（CONV‐IR）相比，对正常组织的损伤更小，这被称为“闪光效应”。它吸引了巨大的研究兴趣，因为它的基本机制是鲜为人知的。本研究的目的是确定是否FLASH-IR和CONV-IR使用修改的临床linac.Materials和methodsAn Elekta Synergy直线加速器诱导不同的炎症细胞因子表达被用来提供6 MeV CONV-IR和修改提供FLASH-IR。将雌性FvB小鼠随机分配到三个不同的组：未辐照对照组、CONV-IR组或FLASH-IR组。通过以20 s间隔手动重复的单脉冲（策略1）或以10 ms间隔的单触发多脉冲（策略2）产生FLASH-IR光束。将小鼠以俯卧位固定在定制设计的施用器中，将Gafchromic膜置于身体下方。小鼠的处方剂量为6至18戈伊，并使用Gafchromic胶片进行验证。三种促炎细胞因子的细胞因子表达（肿瘤坏死因子-α [TNF-α]，干扰素-γ [IFN-γ]，IR后1个月内检查血清样本和皮肤组织中的白细胞介素-6 [IL-6]）和一种抗炎细胞因子（IL-10）。结果改良的直线加速器以约1 × 106戈伊/s的脉冲内剂量率和在源到表面距离（SSD）处超过2戈伊的每个脉冲剂量提供辐射。13到15厘米。在X方向的-20至20 mm范围内达到的剂量覆盖率为最大剂量的90%-105%，在Y方向的-30至30 mm范围内达到的剂量覆盖率为95%。对于6、9、12和15戈伊，通过EBT 3胶片测量的处方剂量和实际剂量之间的绝对偏差分别为2.21%、6.04%、2.09%和2.73%;对于10、14和18戈伊，通过EBT XD胶片测量的处方剂量和实际剂量之间的绝对偏差分别为4.00%、4.49%和2.30%。CONV-IR组与FLASH-IR组相比，D 6时血清中TNF-α、IFN-γ、IL-6和IL-10的降低分别为4.89%、10.28%、− 7.8%和−22.17%; D31时血清中TNF-α、IFN-γ、IL-6和IL-10的降低分别为37.26%、67.16%、56.68%和−18.95%;结论超高剂量率电子闪光可降低血清和皮肤组织中的促炎细胞因子水平，这可能介导了FLASH-IR和CONV-IR之间不同的组织损伤。
PurposeUltra‐high dose rate FLASH irradiation (FLASH‐IR) has been shown to cause less normal tissue damage compared with conventional irradiation (CONV‐IR), this is known as the “FLASH effect.” It has attracted immense research interest because its underlying mechanism is scarcely known. The purpose of this study was to determine whether FLASH‐IR and CONV‐IR induce differential inflammatory cytokine expression using a modified clinical linac.Materials and methodsAn Elekta Synergy linac was used to deliver 6 MeV CONV‐IR and modified to deliver FLASH‐IR. Female FvB mice were randomly assigned to three different groups: a non‐irradiated control, CONV‐IR, or FLASH‐IR. The FLASH‐IR beam was produced by single pulses repeated manually with a 20‐s interval (Strategy 1), or single‐trigger multiple pulses with a 10 ms interval (Strategy 2). Mice were immobilized in the prone position in a custom‐designed applicator with Gafchromic films positioned under the body. The prescribed doses for the mice were 6 to 18 Gy and verified using Gafchromic films. Cytokine expression of three pro‐inflammatory cytokines (tumor necrosis factor‐α [TNF‐α], interferon‐γ [IFN‐γ], interleukin‐6 [IL‐6]) and one anti‐inflammatory cytokine (IL‐10) in serum samples and skin tissue were examined within 1 month post‐IR.ResultsThe modified linac delivered radiation at an intra‐pulse dose rate of around 1 × 106Gy/s and a dose per pulse over 2 Gy at a source‐to‐surface distance (SSD) of 13 to 15 cm. The achieved dose coverage was 90%–105% of the maximum dose within −20 to 20 mm in the X direction and 95% within −30 to 30 mm in the Y direction. The absolute deviations between the prescribed dose and the actual dose were 2.21%, 6.04%, 2.09%, and 2.73% for 6, 9, 12, and 15 Gy as measured by EBT3 films, respectively; and 4.00%, 4.49%, and 2.30% for 10, 14, and 18 Gy as measured by the EBT XD films, respectively. The reductions in the CONV‐IR versus the FLASH‐IR group were 4.89%, 10.28%, −7.8%, and −22.17% for TNF‐α, IFN‐γ, IL‐6, and IL‐10 in the serum on D6, respectively; 37.26%, 67.16%, 56.68%, and −18.95% in the serum on D31, respectively; and 62.67%, 35.65%, 37.75%, and −12.20% for TNF‐α, IFN‐γ, IL‐6, and IL‐10 in the skin tissue, respectively.ConclusionsUltra‐high dose rate electron FLASH caused lower pro‐inflammatory cytokine levels in serum and skin tissue which might mediate differential tissue damage between FLASH‐IR and CONV‐IR.