{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T14:19:26Z","timestamp":1788272366880,"version":"build-2803163510"},"reference-count":77,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["aapm.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Medical Physics"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Preclinical studies have shown that FLASH radiotherapy (FLASH\u2010RT), delivering radiation in ultrahigh dose rates (UHDR), presents reduced healthy tissue toxicity, while maintaining an iso\u2010effective tumor response compared to conventional radiotherapy (CONV\u2010RT). This combined biological benefit was termed as \u201cFLASH effect.\u201d The mechanisms responsible for this effect remain unclear, however, it has been hypothesized that the Fenton reaction which produces  can inflict substantial damage to biomolecules and thus might play a role in the \u201cFLASH effect.\u201d<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>We propose to investigate the influence of radiation delivery parameters including pulse width, dose, dose rate, and initial oxygen concentration on the activation of the Fenton reaction using the Fricke solution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and materials<\/jats:title>\n                    <jats:p>\n                      TOPAS\u2010nBio version 4.0 was used to simulate the radiolysis of the Fricke solution. A cubic water phantom (3\u00a0\u00b5m side) was irradiated laterally by 300 MeV protons. Irradiation was delivered in pulses of tracks with absorbed doses from 1\u201340\u00a0Gy, or in independent tracks. For ultrahigh dose rate (UHDR), we varied the pulse widths between 10\u00a0ns and 10 \u00b5s, corresponding to instantaneous dose rates of 10\n                      <jats:sup>9<\/jats:sup>\n                      \u201310\n                      <jats:sup>5<\/jats:sup>\n                      Gy\/s. For conventional dose rate (CONV), both the independent history approach (mimicking\n                      <jats:sup>6<\/jats:sup>\n                      <jats:sup>0<\/jats:sup>\n                      Co) and multi\u2010pulse irradiations at different frequencies were simulated, yielding a mean dose rate of 0.28\u00a0Gy\/s. Irradiation times reached between 78\u00a0ns\u201085 s. Oxygen concentrations in the equivalent condition of hypoxic and normoxic tissues (1%\u201021%) were considered. The\n                      <jats:italic>G<\/jats:italic>\n                      \u2010value for oxidant ions G(Fe\n                      <jats:sup>3+<\/jats:sup>\n                      ) and \u0394\n                      <jats:italic>G<\/jats:italic>\n                      \u2010value of Fenton reaction (H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      + Fe\n                      <jats:sup>2+\u00a0<\/jats:sup>\n                      \u2192\u00a0Fe\n                      <jats:sup>3+<\/jats:sup>\n                      ++ ) were scored. The simulations ended after G(Fe\n                      <jats:sup>3+<\/jats:sup>\n                      ) achieved steady\u2010state, and calculated yields were compared with published data.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      For CONV, G(Fe\n                      <jats:sup>3+<\/jats:sup>\n                      ) agreed with ICRU\u2010report 34 data within (0.97\u00a0\u00b1\u00a00.1)%. For UHDR, G(Fe\n                      <jats:sup>3+<\/jats:sup>\n                      ) agreed with ICRU data within (1.24\u00a0\u00b1\u00a00.1) % and (0.92\u00a0\u00b1\u00a00.1) % for 5 and 10\u00a0Gy, respectively. Notably, UHDR at 10\u00a0Gy reduced the occurrence of Fenton reactions by 1% and 11.5% at initial oxygen of 21% pO\n                      <jats:sub>2<\/jats:sub>\n                      and 1% pO\n                      <jats:sub>2<\/jats:sub>\n                      , respectively. In consequence, UHDR decreased G(Fe\n                      <jats:sup>3+<\/jats:sup>\n                      ) by 1.8% and 12.5% at these oxygen levels. \u00a0Additionally, increasing the dose per pulse to 40\u00a0Gy further reduced the G(Fe\n                      <jats:sup>3+<\/jats:sup>\n                      ) by 40% at 1%pO\n                      <jats:sub>2<\/jats:sub>\n                      . This effect became negligible for long pulse durations \u226510 \u00b5s and low mean dose rate (0.28\u00a0Gy\/s), highlighting the importance of instantaneous dose rates. Precisely, the decrease was driven by intertrack effects present in UHDR pulses and their impact on the scavenging effect that oxygen had over hydrogen radicals.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The observed reduction in G(Fe\n                      <jats:sup>3<\/jats:sup>\n                      <jats:sup>+<\/jats:sup>\n                      ) is primarily driven by inter\u2010track effects, which limit the availability of radicals participating in Fenton chemistry under UHDR conditions. This effect is most pronounced at low initial oxygen concentrations and minimal at higher oxygen concentrations. The effect is further amplified at higher per\u2010pulse doses (25\u201340\u00a0Gy) but vanishes at long pulse durations and low mean dose rates. This emphasizes the important role of the initial oxygen concentration in UHDR and its influence on the latest activation of Fenton reaction, a mechanism that may contribute to elucidating the FLASH effect.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mp.70576","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T05:42:08Z","timestamp":1786081328000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TOPAS\u2010nBio simulation of the impact of ultrahigh dose rate and oxygen concentration on the Fenton reaction using the Fricke solution"],"prefix":"10.1002","volume":"53","author":[{"given":"M.","family":"Chaoui","sequence":"first","affiliation":[{"name":"Faculty of Sciences University Mohammed V in Rabat Rabat Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. 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