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@ARTICLE{Zhang:292066,
      author       = {T. Zhang$^*$ and C. Stengl$^*$ and L. Derksen and K.
                      Palskis and K. Koritsidis$^*$ and K. Zink and S. Adeberg and
                      G. Major and D. Weishaar and U. Theiß and J. Jin and M. F.
                      Spadea and E. Theodoridou$^*$ and J. Hesser and K.-S.
                      Baumann and J. Seco$^*$},
      title        = {{A}nalysis of hydrogen peroxide production in pure water:
                      {U}ltrahigh versus conventional dose-rate irradiation and
                      mechanistic insights.},
      journal      = {Medical physics},
      volume       = {51},
      number       = {10},
      issn         = {0094-2405},
      address      = {College Park, Md.},
      publisher    = {AAPM},
      reportid     = {DKFZ-2024-01574},
      pages        = {7439-7452},
      year         = {2024},
      note         = {#EA:E041#LA:E041# / 2024 Oct;51(10):7439-7452},
      abstract     = {Ultrahigh 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.},
      keywords     = {hydrogen peroxide (Other) / solvated electron (Other) /
                      ultrahigh dose rate (Other) / water radiolysis (Other)},
      cin          = {E041 / E040},
      ddc          = {610},
      cid          = {I:(DE-He78)E041-20160331 / I:(DE-He78)E040-20160331},
      pnm          = {315 - Bildgebung und Radioonkologie (POF4-315)},
      pid          = {G:(DE-HGF)POF4-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39092902},
      doi          = {10.1002/mp.17335},
      url          = {https://inrepo02.dkfz.de/record/292066},
}