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000292066 1001_ $$0P:(DE-He78)ccee690af64c7540a296cf7268c1dda3$$aZhang, Tengda$$b0$$eFirst author$$udkfz
000292066 245__ $$aAnalysis of hydrogen peroxide production in pure water: Ultrahigh versus conventional dose-rate irradiation and mechanistic insights.
000292066 260__ $$aCollege Park, Md.$$bAAPM$$c2024
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000292066 500__ $$a#EA:E041#LA:E041# / 2024 Oct;51(10):7439-7452
000292066 520__ $$aUltrahigh 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.We 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 ( e aq - ${\mathrm{e}}_{{\mathrm{aq}}}^ - $ ) 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 e aq - ${\mathrm{e}}_{{\mathrm{aq}}}^ - $ and •OH is more sensitive to increased instantaneous ROS concentration by UHDR than a two-order reaction of •OH self-reaction producing H2O2; 2, e aq - ${\mathrm{e}}_{{\mathrm{aq}}}^ - $ has two times higher diffusion coefficient and higher reaction rate constant than that of •OH, which means e aq - ${\mathrm{e}}_{{\mathrm{aq}}}^ - $ 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.H2O2 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 e aq - ${\mathrm{e}}_{{\mathrm{aq}}}^ - $ , 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 e aq - ${\mathrm{e}}_{{\mathrm{aq}}}^ - $ , and bubbled with N2O was irradiated by x-ray to verify the results of low-LET electron beam.UHDR 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.UHDR 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 e aq - ${\mathrm{e}}_{{\mathrm{aq}}}^ - $ , N2O and NaNO3, eliminate the dose-rate dependency of G(H2O2), which suggests e aq - ${\mathrm{e}}_{{\mathrm{aq}}}^ - $ 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.
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000292066 650_7 $$2Other$$ahydrogen peroxide
000292066 650_7 $$2Other$$asolvated electron
000292066 650_7 $$2Other$$aultrahigh dose rate
000292066 650_7 $$2Other$$awater radiolysis
000292066 7001_ $$0P:(DE-He78)5d3fd2061719ec17ba3c894c81dbde89$$aStengl, Christina$$b1$$udkfz
000292066 7001_ $$aDerksen, Larissa$$b2
000292066 7001_ $$aPalskis, Kristaps$$b3
000292066 7001_ $$0P:(DE-He78)28067abbe372c3cab305b09895284468$$aKoritsidis, Konstantinos$$b4$$udkfz
000292066 7001_ $$aZink, Klemens$$b5
000292066 7001_ $$aAdeberg, Sebastian$$b6
000292066 7001_ $$aMajor, Gerald$$b7
000292066 7001_ $$aWeishaar, David$$b8
000292066 7001_ $$aTheiß, Ulrike$$b9
000292066 7001_ $$aJin, Jing$$b10
000292066 7001_ $$aSpadea, Maria Francesca$$b11
000292066 7001_ $$0P:(DE-He78)c632b42c52c39bc800abdbe3924b7dcb$$aTheodoridou, Elpida$$b12$$udkfz
000292066 7001_ $$aHesser, Jürgen$$b13
000292066 7001_ $$aBaumann, Kilian-Simon$$b14
000292066 7001_ $$0P:(DE-He78)102624aca75cfe987c05343d5fdcf2fe$$aSeco, Joao$$b15$$eLast author$$udkfz
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