Development of a portable hypoxia chamber for ultra-high dose rate laser-driven proton radiobiology applications - Archive ouverte HAL Access content directly
Journal Articles Radiation Oncology Year : 2022

Development of a portable hypoxia chamber for ultra-high dose rate laser-driven proton radiobiology applications

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Abstract

Background: There is currently signifcant interest in assessing the role of oxygen in the radiobiological efects at ultra-high dose rates. Oxygen modulation is postulated to play a role in the enhanced sparing efect observed in FLASH radiotherapy, where particles are delivered at 40–1000 Gy/s. Furthermore, the development of laser-driven accelerators now enables radiobiology experiments in extreme regimes where dose rates can exceed 109 Gy/s, and predicted oxygen depletion efects on cellular response can be tested. Access to appropriate experimental enviroments, allowing measurements under controlled oxygenation conditions, is a key requirement for these studies. We report on the development and application of a bespoke portable hypoxia chamber specifcally designed for experiments employing laser-driven sources, but also suitable for comparator studies under FLASH and conventional irradiation conditions. Materials and methods: We used oxygen concentration measurements to test the induction of hypoxia and the maintenance capacity of the chambers. Cellular hypoxia induction was verifed using hypoxia inducible factor-1α immunostaining. Calibrated radiochromic flms and GEANT-4 simulations verifed the dosimetry variations inside and outside the chambers. We irradiated hypoxic human skin fbroblasts (AG01522B) cells with laser-driven protons, conventional protons and reference 225 kVp X-rays to quantify DNA DSB damage and repair under hypoxia. We further measured the oxygen enhancement ratio for cell survival after X-ray exposure in normal fbroblast and radioresistant patient- derived GBM stem cells. Results: Oxygen measurements showed that our chambers maintained a radiobiological hypoxic environment for at least 45 min and pathological hypoxia for up to 24 h after disconnecting the chambers from the gas supply. We observed a signifcant reduction in the 53BP1 foci induced by laser-driven protons, conventional protons and X-rays in the hypoxic cells compared to normoxic cells at 30 min post-irradiation. Under hypoxic irradiations, the Laser-driven
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Dates and versions

hal-03833587 , version 1 (28-10-2022)

Licence

Attribution - CC BY 4.0

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Cite

Pankaj Chaudhary, Deborah C Gwynne, Boris Odlozilik, Aaron Mcmurray, Giuliana Milluzzo, et al.. Development of a portable hypoxia chamber for ultra-high dose rate laser-driven proton radiobiology applications. Radiation Oncology, 2022, 17, pp.77. ⟨10.1186/s13014-022-02024-3⟩. ⟨hal-03833587⟩
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