辐射在癌症治疗中的放射生物学有效性可以在不同尺度（分子至器官尺度）和辐射后不同时间进行研究。水辐射分解过程中自由基和活性氧的产生对于理解在观察到的生物学结果中发挥作用的基本机制特别相关。集成辐射后物理、物理化学和化学阶段模拟的蒙特卡罗工具的开发和验证对于维持实验非常重要。因此，在本研究中，我们建议通过模拟验证新的 Geant4-DNA 化学模块在质子临床前束线上进行水辐射分解和 Fricke 剂量测定实验。在本研究中，我们使用 GATE 蒙特卡罗模拟平台（版本 9.3）模拟 ARRONAX 等时回旋加速器 (IBA Cyclone 70XP) 在常规条件下产生的 67.5 MeV 质子束剂量率（0.2 Gy/s）模拟超纯液态水样品和弗里克剂量计的辐照。我们将深度剂量分布与平面平行 Advanced PTW 34045 Markus 电离室进行的测量进行了比较。然后，Geant4 版本 11.2 提出的新 Geant4-DNA 化学应用已用于评估 HO • ${\mathrm{HO}}^ \bullet $ , e aq - ${\mathrm{e}}_{ {\mathrm{aq}}}^ - $ , H 3 O ${{\mathrm{H}}}_3{{\mathrm{O}}}^ $ , H 2 O 2 ${{\mathrm{H} }}_2{{\mathrm{O}}}_2$ , H 2 ${{\mathrm{H}}}_2$ , HO 2 • ${\mathrm{HO}}_2^ \bullet $ , HO 2 - , O 2 • - ${\mathrm{HO}}_2^ - ,{\mathrm{\ O}}_2^{ \bullet - }$ 和 HO - ${\mathrm{HO}}^ - $ 反应物种时间直到照射后1小时。特别是，通过与 H 2 O 2 ${{\mathrm{H}}}_2{{\mathrm{O}}}_2$ 和 Fe3 的辐射分解产率的实验测量值进行比较，研究了氧气和 pH 值的影响。 GATE 模拟再现了液态水中的深度剂量分布，误差在 4% 以内。使用 Geant4-DNA，我们能够重现实验性 H 2 O 2 ${{\mathrm{H}}}_2{{\mathrm{O}}}_2$ 在通气和脱气条件下辐照后 1 小时的辐射分解产量，显示氧气浓度的微小变化对物种进化的影响。对于 Fricke 剂量计，模拟 G(Fe3 ) 为 15.97 ± 0.2 分子/100 eV，比测量值（14.4 ± 04 分子/100 eV）高 11%。这些结果旨在通过涉及其他辐射分解物质的新比较来巩固，例如 e aq - ${\mathrm{e}}_{{\mathrm{aq}}}^ - $ 或 , O 2 • - $,{\mathrm{\ O}}_2^{ \bullet - } $ 进一步研究超高剂量率 (UHDR) 下观察到的 FLASH 效应的机制。© 2024 美国医学物理学家协会。

Radiobiological effectiveness of radiation in cancer treatment can be studied at different scales (molecular till organ scale) and different time post irradiation. The production of free radicals and reactive oxygen species during water radiolysis is particularly relevant to understand the fundamental mechanisms playing a role in observed biological outcomes. The development and validation of Monte Carlo tools integrating the simulation of physical, physico-chemical and chemical stages after radiation is very important to maintain with experiments.Therefore, in this study, we propose to validate a new Geant4-DNA chemistry module through the simulation of water radiolysis and Fricke dosimetry experiments on a proton preclinical beam line.In this study, we used the GATE Monte Carlo simulation platform (version 9.3) to simulate a 67.5 MeV proton beam produced with the ARRONAX isochronous cyclotron (IBA Cyclone 70XP) at conventional dose rate (0.2 Gy/s) to simulate the irradiation of ultra-pure liquid water samples and Fricke dosimeter. We compared the depth dose profile with measurements performed with a plane parallel Advanced PTW 34045 Markus ionization chamber. Then, a new Geant4-DNA chemistry application proposed from Geant4 version 11.2 has been used to assess the evolution of HO • ${\mathrm{HO}}^ \bullet $ , e aq - ${\mathrm{e}}_{{\mathrm{aq}}}^ - $ , H 3 O + ${{\mathrm{H}}}_3{{\mathrm{O}}}^ + $ , H 2 O 2 ${{\mathrm{H}}}_2{{\mathrm{O}}}_2$ , H 2 ${{\mathrm{H}}}_2$ , HO 2 • ${\mathrm{HO}}_2^ \bullet $ , HO 2 - , O 2 • - ${\mathrm{HO}}_2^ - ,{\mathrm{\ O}}_2^{ \bullet - }$ and HO - ${\mathrm{HO}}^ - $ reactive species along time until 1-h post-irradiation. In particular, the effect of oxygen and pH has been investigated through comparisons with experimental measurements of radiolytic yields for H 2 O 2 ${{\mathrm{H}}}_2{{\mathrm{O}}}_2$ and Fe3+.GATE simulations reproduced, within 4%, the depth dose profile in liquid water. With Geant4-DNA, we were able to reproduce experimental H 2 O 2 ${{\mathrm{H}}}_2{{\mathrm{O}}}_2$ radiolytic yields 1-h post-irradiation in aerated and deaerated conditions, showing the impact of small changes in oxygen concentrations on species evolution along time. For the Fricke dosimeter, simulated G(Fe3+) is 15.97 ± 0.2 molecules/100 eV which is 11% higher than the measured value (14.4 ± 04 molecules/100 eV).These results aim to be consolidated by new comparisons involving other radiolytic species, such as e aq - ${\mathrm{e}}_{{\mathrm{aq}}}^ - $ or , O 2 • - $,{\mathrm{\ O}}_2^{ \bullet - }$ to further study the mechanisms underlying the FLASH effect observed at ultra-high dose rates (UHDR).© 2024 American Association of Physicists in Medicine.