Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin.
Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire.
Int J Radiat Oncol Biol Phys. 2024 Jan 1;118(1):262-267. doi: 10.1016/j.ijrobp.2023.07.042. Epub 2023 Aug 7.
: Investigations into ultra-high dose rate (UHDR) radiotherapy have dramatically risen because of the observed normal tissue sparing FLASH effect without sacrificing tumor control. The purpose of this study was to provide a direct beamline comparison of protons and electrons to determine where UHDR to conventional dose rates (CDR) changes affect the resultant radiochemistry.
: We used well characterized assays of reactive oxygen species (ROS) and oxygen consumption to assess the radiolysis in protein solutions. Three optical reporters related to ROS (CellROX Deep Red, reflects highly reactive radicals; Amplex Red reflects HO; and Oxyphor reflects partial pressure loss (ΔpO)). A Varian ProBeam proton cyclotron and a converted Varian Trilogy electron linac were used for irradiation at both their CDR and UHDR capable level, to assess the assay change per unit dose.
: For both protons and electrons an expected reduction in ROS was noted going from CDR to UHDR, and results interpreted as a reduction in the ratio of UHDR/CDR yield. The CellROX assay showed no difference between beamlines, each showing ~80% reduction in ROS from CDR to UHDR. The Amplex assay showed the largest inter-beamline difference, with ~5% loss using protons vs ~69% loss with electrons, in protein solution. The Oxyphor assay of ΔpO showed a small difference in CDR to UHDR with a 23% loss with protons and 43% loss with electrons.
: Interpretation of ROS assays and oxygen consumption is notoriously challenging. These assays might be interpreted by their most activating species’ lifetime. The assay for highly reactive OH●, appeared independent of beamline, whereas the assays for the longer lived HO species and ΔpO assay showed differences between beamlines via the UHDR/CDR ratio. This work can be used for FLASH hypothesis testing by comparing these assays to isodose biological FLASH effects in vivo.
由于观察到的正常组织保护 FLASH 效应，而不牺牲肿瘤控制，超高剂量率（UHDR）放射治疗的研究急剧增加。本研究的目的是提供质子和电子的直接射束线比较，以确定 UHDR 对常规剂量率（CDR）变化如何影响所得放射化学。
我们使用经过良好表征的活性氧（ROS）和耗氧量测定来评估蛋白质溶液中的放射分解。三种与 ROS 相关的光学报告器（CellROX Deep Red，反映高反应性自由基；Amplex Red 反映 HO；和 Oxyphor 反映分压损失（ΔpO））。使用瓦里安 ProBeam 质子回旋加速器和经过改造的瓦里安 Trilogy 电子直线加速器，在其 CDR 和 UHDR 能力水平下进行照射，以评估单位剂量的测定变化。
对于质子和电子，从 CDR 到 UHDR 都观察到 ROS 预期减少，结果解释为 UHDR/CDR 产额的减少。CellROX 测定法在光束线上没有差异，每个光束线均显示 ROS 从 CDR 到 UHDR 的减少约 80%。Amplex 测定法显示出最大的光束线之间差异，在蛋白质溶液中，使用质子时约有 5%的 ROS 损失，而使用电子时则有约 69%的 ROS 损失。Oxyphor 测定法的 ΔpO 在 CDR 到 UHDR 之间显示出较小的差异，质子损失 23%，电子损失 43%。
ROS 测定法和耗氧量的解释是出了名的具有挑战性。这些测定法可能根据其最激活的物种的寿命进行解释。对于高反应性 OH●的测定法，似乎与光束线无关，而对于寿命较长的 HO 物种的测定法和 ΔpO 测定法，则通过 UHDR/CDR 比值显示出光束线之间的差异。这项工作可以通过将这些测定法与体内等剂量生物学 FLASH 效应进行比较，用于 FLASH 假设检验。
