Analysis of hydrogen peroxide production in pure water: Ultrahigh versus conventional dose‐rate irradiation and mechanistic insights

Author:

Zhang Tengda12,Stengl Christina34,Derksen Larissa5,Palskis Kristaps67,Koritsidis Konstantinos18,Zink Klemens5910,Adeberg Sebastian91011,Major Gerald121314,Weishaar David5,Theiß Ulrike1015,Jin Jing1617,Spadea Maria Francesca18,Theodoridou Elpida18,Hesser Jürgen219,Baumann Kilian‐Simon5910,Seco Joao120

Affiliation:

1. Division of Biomedical Physics in Radiation Oncology German Cancer Research Center Heidelberg Germany

2. MIISM, Medical Faculty Mannheim Heidelberg University Mannheim Germany

3. Division of Medical Physics in Radiation Oncology German Cancer Research Center Heidelberg Germany

4. Medical Faculty Heidelberg Heidelberg University Heidelberg Germany

5. University of Applied Sciences Institute of Medical Physics and Radiation Protection Giessen Germany

6. CERN Geneva Switzerland

7. Riga Technical University Riga Latvia

8. Faculty of Physics The Aristotle University of Thessaloniki Thessaloniki Greece

9. Department of Radiotherapy and Radiation Oncology Marburg University Hospital Marburg Germany

10. Marburg Ion‐Beam Therapy Center (MIT) Marburg Germany

11. Universitäres Centrum für Tumorerkrankungen (UCT) Frankfurt ‐ Marburg Marburg Germany

12. Department of Radiation Oncology Heidelberg University Hospital Heidelberg Germany

13. Heidelberg Institute of Radiation Oncology (HIRO) Heidelberg Germany

14. National Center for Tumor Diseases (NCT) Heidelberg Germany

15. Department of Radiotherapy and Radiation Oncology Philipps‐University Marburg Germany

16. State Key Laboratory of Molecular Oncology and Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC) Beijing China

17. Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, CAMS and PUMC Shenzhen China

18. Institute of Biomedical Engineering Karlsruhe Institute of Technology (KIT) Karlsruhe Germany

19. Interdisciplinary Center for Scientific Computing (IWR) Central Institute for Computer Engineering (ZITI) CZS Heidelberg Center for Model‐Based AI Heidelberg University Heidelberg Germany

20. Department of Physics and Astronomy Heidelberg University Heidelberg Germany

Abstract

AbstractBackgroundUltrahigh dose‐rate radiation (UHDR) produces less hydrogen peroxide (H2O2) in pure water, as suggested by some experimental studies, and is used as an argument for the validity of the theory that FLASH spares the normal tissue due to less reactive oxygen species (ROS) production. In contrast, most Monte Carlo simulation studies suggest the opposite.PurposeWe aim to unveil the effect of UHDR on H2O2 production in pure water and its underlying mechanism, to serve as a benchmark for Monte Carlo simulation. We hypothesized that the reaction of solvated electrons () removing hydroxyl radicals (•OH), the precursor of H2O2, is the reason why UHDR leads to a lower G‐value (molecules/100 eV) for H2O2 (G[H2O2]), because: 1, the third‐order reaction between and •OH is more sensitive to increased instantaneous ROS concentration by UHDR than a two‐order reaction of •OH self‐reaction producing H2O2; 2, has two times higher diffusion coefficient and higher reaction rate constant than that of •OH, which means would dominate the competition for •OH and benefit more from the inter‐track effect of UHDR. Meanwhile, we also experimentally verify the theory of long‐lived radicals causing lower G(H2O2) in conventional irradiation, which is mentioned in some simulation studies.Methods and materialsH2O2 was measured by Amplex UltraRed assay. 430.1 MeV/u carbon ions (50 and 0.1 Gy/s), 9 MeV electrons (600 and 0.62 Gy/s), and 200 kV x‐ray tube (10 and 0.1 Gy/s) were employed. For three kinds of water (real hypoxic: 1% O2; hypoxic: 1% O2 and 5% CO2; and normoxic: 21% O2), unbubbled and bubbled samples with N2O, the scavenger of , were irradiated by carbon ions and electrons with conventional and UHDR at different absolute dose levels. Normoxic water dissolved with sodium nitrate (NaNO3), another scavenger of , and bubbled with N2O was irradiated by x‐ray to verify the results of low‐LET electron beam.ResultsUHDR leads to a lower G(H2O2) than conventional irradiation. O2 and CO2 can both increase G(H2O2). N2O increases G(H2O2) of both UHDR and conventional irradiation and eliminates the difference between them for carbon ions. However, N2O decreases G(H2O2) in electron conventional irradiation but increases G(H2O2) in the case of UHDR, ending up with no dose‐rate dependency of G(H2O2). Three‐spilled carbon UHDR does not have a lower G(H2O2) than one‐spilled UHDR. However, the electron beam shows a lower G(H2O2) for three‐spilled UHDR than for one‐spilled UHDR. Normoxic water with N2O or NaNO3 can both eliminate the dose rate dependency of H2O2 production for x‐ray.ConclusionsUHDR has a lower G(H2O2) than the conventional irradiation for both high LET carbon and low LET electron and x‐ray beams. Both scavengers for , N2O and NaNO3, eliminate the dose‐rate dependency of G(H2O2), which suggests is the reason for decreased G(H2O2) for UHDR. Three‐spilled UHDR versus one‐spilled UHDR indicates that the assumption of residual radicals reducing G(H2O2) of conventional irradiation may only be valid for low LET electron beam.

Funder

Bundesministerium für Bildung und Forschung

Publisher

Wiley

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3