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