研究动态
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质子和电子的UHDR等剂量照射产生的短寿命ROS产量相似,但长寿命物种的产量有所不同。

Proton and electron UHDR isodose irradiations produce similar short-lived ROS yields with differing longer-lived species yields.

发表日期:2023 Aug 07
作者: William Thomas, Jacob Sunnerberg, Matthew Reed, David J Gladstone, Rongxiao Zhang, Joseph Harms, Harold M Swartz, Brian W Pogue
来源: Int J Radiat Oncol

摘要:

由于观察到在不损害肿瘤控制的情况下,可以保存正常组织的FLASH效应,对超高剂量率(UHDR)放射治疗的研究急剧增加。本研究的目的是直接比较质子和电子的束流,以确定UHDR 对常规剂量率(CDR)的变化如何影响放射化学反应。我们使用了良好表征的反应氧化物种(ROS)和氧耗来评估蛋白质溶液中的辐解。与ROS相关的三种光学标记物(CellROX Deep Red反映高活性自由基;Amplex Red反映H2O2;Oxyphor反映部分氧气压力损失(ΔpO2))。Varian ProBeam质子回旋加速器和改装的Varian Trilogy电子直线加速器用于在它们的CDR和UHDR能力水平进行照射,以评估单位剂量下的反应变化。对于质子和电子来说,从CDR到UHDR观察到了ROS的预期减少,并将结果解释为UHDR/CDR产生率的减少。CellROX反应显示束流之间没有差异,每个束流从CDR到UHDR的ROS减少了约80%。Amplex反应显示了最大的束流之间差异,用质子约有5%的损失,而用电子约有69%的损失,这是在蛋白质溶液中。ΔpO2的Oxyphor反应在CDR到UHDR时显示了一小部分的差异,其中质子损失了23%,而电子损失了43%。解释ROS反应和氧气消耗是极具挑战性的。这些反应可以通过它们最活跃物种的寿命进行解释。对于高活性的OH●物种反应,不受束流影响,而寿命较长的H2O2物种和DpO2反应则显示了束流之间的差异通过UHDR/CDR比率。通过将这些反应与体内等剂量生物FLASH效应进行比较,可以用于对FLASH假设进行测试。版权所有 © 2023. 由Elsevier Inc.发表。
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 H2O2; and Oxyphor reflects partial pressure loss (ΔpO2)). 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 ΔpO2 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 H2O2 species and DpO2 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.Copyright © 2023. Published by Elsevier Inc.