FLASH radiotherapy is a novel technique that has been shown in numerous preclinical in vivo studies to have the potential to be the next important improvement in cancer treatment. However, the biological mechanisms responsible for the selective FLASH sparing effect of normal tissues are not yet known. An optimal translation of FLASH radiotherapy into the clinic would require a good understanding of the specific beam parameters that induces a FLASH effect, environmental conditions affecting the response, and the radiobiological mechanisms involved. Even though the FLASH effect has generally been considered as an in vivo effect, studies finding these answers would be difficult and ethically challenging to carry out solely in animals. Hence, suitable in vitro studies aimed towards finding these answers are needed. In this review, we describe and summarise several in vitro assays that have been used or could be used to finally elucidate the mechanisms behind the FLASH effect.
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| http://dx.doi.org/10.1017/erm.2022.5 | DOI Listing |
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FLASH radiotherapy: mechanisms, nanotherapeutic strategy and future development.
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Department of Pharmacy, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital of Wannan Medical College Wuhu China
Ultra-high dose-rate (FLASH) radiotherapy serves as an ideal procedure to treat tumors efficiently without harming normal tissues and has demonstrated satisfactory antitumor effects in multiple animal tumor models. However, the biological mechanisms of FLASH radiotherapy have not yet been fully elucidated, and the small number of devices delivering FLASH dose rate has limited its wide application. This review summarizes the possible biological mechanisms and antitumor effects of FLASH radiotherapy, its application in nanotherapeutic strategy, as well as its challenges and future development.
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Department of Oncology Radiation, University of California San Francisco, 1600 Divisadero Street, Suite HM006, San Francisco, California, 94143, UNITED STATES.
To study the effect of dose-rate in the time evolution of chemical yields produced in pure water versus a cellular-like environment for FLASH radiotherapy research. A version of TOPAS-nBio with Tau-Leaping algorithm was used to simulate the homogenous chemistry stage of water radiolysis using three chemical models: 1) liquid water model that considered scavenging of eaq-, H● by dissolved oxygen; 2) Michaels & Hunt model that considered scavenging of ●OH, eaq-, and H● by biomolecules existing in cellular environment; 3) Wardman model that considered model 2) and the chemical repair enzyme glutathione (GHS). H2O2 concentrations at conventional and FLASH dose-rates were compared with published measurements.
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