对不同辐射束参数设置如何影响 FLASH 效应的诱导和程度的理解仍然有限。我们试图系统地评估辐射引起的胃肠道 (GI) 毒性 (RIGIT) 的程度如何取决于平均剂量率 ( MDR）和每脉冲剂量（DPP）。C57BL/6J 小鼠通过传统照射（低 DPP 和低 MDR，CONV）或通过 DPP 和 MDR 的各种组合接受总腹部照射（11-14 Gy，单次）超高剂量率 (UHDR) 光束条件。评估1 Gy至6 Gy范围内的DPP，同时保持总剂量和MDR（> 100 Gy/s）恒定；在总剂量和 DPP 保持恒定的情况下，在 0.3-1440 Gy/s 范围内评估 MDR 的影响。通过再生隐窝测定和生存评估对非荷瘤小鼠的 RIGIT 进行量化。通过肿瘤生长延迟来评估肿瘤反应。在使用恒定 MDR (>100 Gy/s) 的每次测试总剂量内，增加 DPP 导致保留增加（再生隐窝数量增加），效果更显着12 和 14 Gy TAI。有趣的是，在 > 4 Gy 的 DPP 下，无论使用何种 MDR（从 0.3 至 1440 Gy/s），都表现出相似的隐窝保护水平。在 4.7 Gy 的固定高 DPP 下，无论 MDR 如何，存活率相对于 CONV 均得到同等改善。然而，在 0.93 Gy 的较低 DPP 下，与 0.3 Gy/s 相比，104 Gy/s 的 MDR 产生的生存效果更大。我们还使用临床相关的黑色素瘤小鼠模型证实，无论 MDR 如何，高 DPP 都会产生与 CONV 相同程度的肿瘤生长延迟。这项研究证明了光束参数设置对 FLASH 效应程度的强烈影响。高 DPP 和 UHDR 似乎都足以独立产生 FLASH，避免胃肠道毒性，同时在所有条件下都保持等有效的肿瘤反应。版权所有 © 2024。由 Elsevier Inc. 出版。

The understanding of how varying radiation beam parameter settings affect the induction and magnitude of the FLASH effect remains limited.We sought to systematically evaluate how the magnitude of radiation-induced gastrointestinal (GI) toxicity (RIGIT) depends on the interplay between mean dose rate (MDR) and dose per pulse (DPP).C57BL/6J mice received total abdominal irradiation (11-14 Gy, single fraction) through either conventional irradiation (low DPP and low MDR, CONV) or through various combinations of DPP and MDR up to ultra-high-dose-rate (UHDR) beam conditions. DPPs ranging from 1 Gy to 6 Gy were evaluated while the total dose and MDR (>100 Gy/s) were kept constant; the effects of MDR were evaluated for the range 0.3-1440 Gy/s while the total dose and DPP were kept constant. RIGIT was quantified in non-tumor-bearing mice through the regenerating crypt assay and survival assessment. Tumor response was evaluated through tumor growth delay.Within each tested total dose using a constant MDR (>100 Gy/s), increasing DPP led to an increase in sparing (an increase in number of regenerating crypts), with a more prominent effect seen at 12 and 14 Gy TAI. Interestingly, at DPPs of >4 Gy, similar level of crypt sparing was demonstrated irrespective of the MDR used (from 0.3 to 1440 Gy/s). At a fixed high DPP of 4.7 Gy, survival was equivalently improved relative to CONV irrespective of MDR. However, at a lower DPP of 0.93 Gy, a MDR of 104 Gy/s produced a greater survival effect compared to 0.3 Gy/s. We also confirmed that high DPP, regardless of MDR, produced the same magnitude of tumor growth delay relative to CONV using a clinically relevant melanoma mouse model.This study demonstrates the strong influence that the beam parameter settings have on the magnitude of the FLASH effect. Both high DPP and UHDR appeared independently sufficient to produce FLASH sparing of GI toxicity, while isoeffective tumor response was maintained across all conditions.Copyright © 2024. Published by Elsevier Inc.