Abstract：
BACKGROUND: 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.
OBJECTIVE: 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.
METHODS: 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+.
RESULTS: 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).
CONCLUSIONS: 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).
OBJECTIVE: 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.
METHODS: 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+.
RESULTS: 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).
CONCLUSIONS: 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).
摘要：
背景：可以在不同的尺度（分子直到器官尺度）和照射后的不同时间研究放射在癌症治疗中的放射生物学有效性。水辐射分解过程中自由基和活性氧的产生与理解在观察到的生物学结果中起作用的基本机制特别相关。蒙特卡罗工具的开发和验证集成了物理模拟，辐射后的物理化学和化学阶段对实验保持非常重要。
目标：因此，在这项研究中，我们建议通过在质子临床前束线上模拟水放射分解和Fricke剂量测定实验来验证新的Geant4-DNA化学模块。
方法：在本研究中，我们使用GATEMonteCarlo模拟平台（9.3版）模拟了用ARRONAX等时回旋加速器（IBACyclone70XP）以常规剂量率（0.2Gy/s）产生的67.5MeV质子束，以模拟超纯液态水样品和Fricke剂量计的辐照。我们将深度剂量分布与使用平面平行的高级PTW34045Markus电离室进行的测量进行了比较。然后，从Geant4版本11.2提出的新的Geant4-DNA化学应用程序已用于评估HO•${\\mathrm{HO}}^\\bullet$的演变，eaq-${\\mathrm{e}}_{{\\mathrm{aq}}}^-$，H3O+${\\mathrm{H}}}_3{{\\mathrm{O}}}^+$,H2O2${\\mathrm{H}}}_2{{\\mathrm{O}}}_2$,H2${{\\mathrm{H}}}_2$,HO2•${\\mathrm{HO}}_2^\\bullet$，HO2-,O2•-${\\mathrm{HO}}_2^-，{\\mathrm{\\O}}_2^{\\bullet-}$和HO-${\\mathrm{HO}}^-反应性物种沿着时间直到辐照后1小时。特别是,通过与H2O2${{\\mathrm{H}}}_2{{\\mathrm{O}}}_2$和Fe3+的放射产率的实验测量结果进行比较，研究了氧气和pH值的影响。
结果：复制了GATE模拟，4%以内,液态水中的深度剂量曲线。有了Geant4-DNA,我们能够重现实验H2O2${{\\mathrm{H}}}_2{{\\mathrm{O}}}_2$在曝气和脱气条件下辐照后1小时的辐射分解产量,显示氧气浓度的微小变化对物种随时间进化的影响。对于Fricke剂量计,模拟G（Fe3）为15.97±0.2分子/100eV，比测量值（14.4±04分子/100eV）高11％。
结论：这些结果旨在通过涉及其他放射性物种的新比较来巩固，例如eaq-${\\mathrm{e}}_{\\mathrm{aq}}^-$或，O2•-$，{\\mathrm{\\O}}_2^{\\bullet-}$进一步研究在超高剂量率(UHDR)下观察到的FLASH效应的潜在机制。
目标：因此，在这项研究中，我们建议通过在质子临床前束线上模拟水放射分解和Fricke剂量测定实验来验证新的Geant4-DNA化学模块。
方法：在本研究中，我们使用GATEMonteCarlo模拟平台（9.3版）模拟了用ARRONAX等时回旋加速器（IBACyclone70XP）以常规剂量率（0.2Gy/s）产生的67.5MeV质子束，以模拟超纯液态水样品和Fricke剂量计的辐照。我们将深度剂量分布与使用平面平行的高级PTW34045Markus电离室进行的测量进行了比较。然后，从Geant4版本11.2提出的新的Geant4-DNA化学应用程序已用于评估HO•${\\mathrm{HO}}^\\bullet$的演变，eaq-${\\mathrm{e}}_{{\\mathrm{aq}}}^-$，H3O+${\\mathrm{H}}}_3{{\\mathrm{O}}}^+$,H2O2${\\mathrm{H}}}_2{{\\mathrm{O}}}_2$,H2${{\\mathrm{H}}}_2$,HO2•${\\mathrm{HO}}_2^\\bullet$，HO2-,O2•-${\\mathrm{HO}}_2^-，{\\mathrm{\\O}}_2^{\\bullet-}$和HO-${\\mathrm{HO}}^-反应性物种沿着时间直到辐照后1小时。特别是,通过与H2O2${{\\mathrm{H}}}_2{{\\mathrm{O}}}_2$和Fe3+的放射产率的实验测量结果进行比较，研究了氧气和pH值的影响。
结果：复制了GATE模拟，4%以内,液态水中的深度剂量曲线。有了Geant4-DNA,我们能够重现实验H2O2${{\\mathrm{H}}}_2{{\\mathrm{O}}}_2$在曝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随时间进化的影响。对于Fricke剂量计,模拟G（Fe3）为15.97±0.2分子/100eV，比测量值（14.4±04分子/100eV）高11％。
结论：这些结果旨在通过涉及其他放射性物种的新比较来巩固，例如eaq-${\\mathrm{e}}_{\\mathrm{aq}}^-$或，O2•-$，{\\mathrm{\\O}}_2^{\\bullet-}$进一步研究在超高剂量率(UHDR)下观察到的FLASH效应的潜在机制。
