May oxygen depletion explain the FLASH effect? A chemical track structure analysis.

Autor: Boscolo D; GSI Helmholtzzentrum für Schwerionenforschung GmbH, Darmstadt, Germany., Scifoni E; Trento Institute for Fundamental Physics and Applications (TIFPA), National Institute for Nuclear Physics (INFN), Trento, Italy., Durante M; GSI Helmholtzzentrum für Schwerionenforschung GmbH, Darmstadt, Germany; Institut für Physik Kondensierter Materie, Technische Universität Darmstadt, Germany. Electronic address: m.durante@gsi.de., Krämer M; GSI Helmholtzzentrum für Schwerionenforschung GmbH, Darmstadt, Germany., Fuss MC; GSI Helmholtzzentrum für Schwerionenforschung GmbH, Darmstadt, Germany. Electronic address: m.fuss@gsi.de.
Jazyk: angličtina
Zdroj: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology [Radiother Oncol] 2021 Sep; Vol. 162, pp. 68-75. Date of Electronic Publication: 2021 Jun 29.
DOI: 10.1016/j.radonc.2021.06.031
Abstrakt: Background and Purpose: Recent observations in animal models show that ultra-high dose rate ("FLASH") radiation treatment significantly reduces normal tissue toxicity maintaining an equivalent tumor control. The dependence of this "FLASH" effect on target oxygenation has led to the assumption that oxygen "depletion" could be its major driving force.
Materials and Methods: In a bottom-up approach starting from the chemical track evolution of 1 MeV electrons in oxygenated water simulated with the TRAX-CHEM Monte Carlo code, we determine the oxygen consumption and radiolytic reactive oxygen species production following a short radiation pulse. Based on these values, the effective dose weighted by oxygen enhancement ratio (OER) or the in vitro cell survival under dynamic oxygen pressure is calculated and compared to that of conventional exposures, at constant OER.
Results: We find an excellent agreement of our Monte Carlo predictions with the experimental value for radiolytic oxygen removal from oxygenated water. However, the application of the present model to published radiobiological experiment conditions shows that oxygen depletion can only have a negligible impact on radiosensitivity through oxygen enhancement, especially at typical experimental oxygenations where a FLASH effect has been observed.
Conclusion: We show that the magnitude and dependence of the "oxygen depletion" hypothesis are not consistent with the observed biological effects of FLASH irradiation. While oxygenation plays an undoubted role in mediating the FLASH effect, we conclude that state-of-the-art radiation chemistry models do not support oxygen depletion and radiation-induced transient hypoxia as the main mechanism.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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