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

Autor: Chaudhary P; The Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Lisburn Road, Belfast, BT9 7AE, Northern Ireland, UK. p.chaudhary@qub.ac.uk.; Centre for Plasma Physics, School of Mathematics and Physics, Queen's University Belfast, Belfast, BT7 1NN, Northern Ireland, UK. p.chaudhary@qub.ac.uk., Gwynne DC; Centre for Plasma Physics, School of Mathematics and Physics, Queen's University Belfast, Belfast, BT7 1NN, Northern Ireland, UK., Odlozilik B; Centre for Plasma Physics, School of Mathematics and Physics, Queen's University Belfast, Belfast, BT7 1NN, Northern Ireland, UK.; ELI-Beamlines Centre, Institute of Physics, Czech Academy of Sciences, Za Radnicí 835, 252 41, Dolní Břežany, Czech Republic., McMurray A; Centre for Plasma Physics, School of Mathematics and Physics, Queen's University Belfast, Belfast, BT7 1NN, Northern Ireland, UK., Milluzzo G; Centre for Plasma Physics, School of Mathematics and Physics, Queen's University Belfast, Belfast, BT7 1NN, Northern Ireland, UK.; Laboratori Nazionali del Sud - Istituto Nazionale di Fisica Nucleare, Via S Sofia 62, 95123, Catania, Italy., Maiorino C; The Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Lisburn Road, Belfast, BT9 7AE, Northern Ireland, UK., Doria D; Centre for Plasma Physics, School of Mathematics and Physics, Queen's University Belfast, Belfast, BT7 1NN, Northern Ireland, UK.; Extreme Light Infrastructure (ELI-NP) and Horia Hulubei National Institute for R & D in Physics and Nuclear Engineering (IFIN-HH), Str. Reactorului No. 30, 077125, Bucharest, Magurele, Romania., Ahmed H; Centre for Plasma Physics, School of Mathematics and Physics, Queen's University Belfast, Belfast, BT7 1NN, Northern Ireland, UK.; Experimental Science Group, Central Laser Facility, Rutherford Appleton Laboratory, Didcot, Oxford, OX11 0QX, England, UK., Romagnani L; Laboratoire LULI, École Polytechnique, Route de Saclay, 91128, Palaiseau, Paris, France., Alejo A; Centre for Plasma Physics, School of Mathematics and Physics, Queen's University Belfast, Belfast, BT7 1NN, Northern Ireland, UK., Padda H; Department of Physics, SUPA, University of Strathclyde, Glasgow, G1 1XQ, Scotland, UK., Green J; Experimental Science Group, Central Laser Facility, Rutherford Appleton Laboratory, Didcot, Oxford, OX11 0QX, England, UK., Carroll D; Experimental Science Group, Central Laser Facility, Rutherford Appleton Laboratory, Didcot, Oxford, OX11 0QX, England, UK., Booth N; Experimental Science Group, Central Laser Facility, Rutherford Appleton Laboratory, Didcot, Oxford, OX11 0QX, England, UK., McKenna P; Department of Physics, SUPA, University of Strathclyde, Glasgow, G1 1XQ, Scotland, UK., Kar S; Centre for Plasma Physics, School of Mathematics and Physics, Queen's University Belfast, Belfast, BT7 1NN, Northern Ireland, UK., Petringa G; Laboratori Nazionali del Sud - Istituto Nazionale di Fisica Nucleare, Via S Sofia 62, 95123, Catania, Italy., Catalano R; Laboratori Nazionali del Sud - Istituto Nazionale di Fisica Nucleare, Via S Sofia 62, 95123, Catania, Italy., Cammarata FP; Laboratori Nazionali del Sud - Istituto Nazionale di Fisica Nucleare, Via S Sofia 62, 95123, Catania, Italy., Cirrone GAP; Laboratori Nazionali del Sud - Istituto Nazionale di Fisica Nucleare, Via S Sofia 62, 95123, Catania, Italy., McMahon SJ; The Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Lisburn Road, Belfast, BT9 7AE, Northern Ireland, UK., Prise KM; The Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Lisburn Road, Belfast, BT9 7AE, Northern Ireland, UK. k.prise@qub.ac.uk., Borghesi M; Centre for Plasma Physics, School of Mathematics and Physics, Queen's University Belfast, Belfast, BT7 1NN, Northern Ireland, UK. M.Borghesi@qub.ac.uk.
Jazyk: angličtina
Zdroj: Radiation oncology (London, England) [Radiat Oncol] 2022 Apr 15; Vol. 17 (1), pp. 77. Date of Electronic Publication: 2022 Apr 15.
DOI: 10.1186/s13014-022-02024-3
Abstrakt: Background: There is currently significant interest in assessing the role of oxygen in the radiobiological effects at ultra-high dose rates. Oxygen modulation is postulated to play a role in the enhanced sparing effect 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 10 9  Gy/s, and predicted oxygen depletion effects 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 specifically 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 verified using hypoxia inducible factor-1α immunostaining. Calibrated radiochromic films and GEANT-4 simulations verified the dosimetry variations inside and outside the chambers. We irradiated hypoxic human skin fibroblasts (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 fibroblast 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 significant 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 protons induced significant residual DNA DSB damage in hypoxic AG01522B cells compared to the conventional dose rate protons suggesting an important impact of these extremely high dose-rate exposures. We obtained an oxygen enhancement ratio (OER) of 2.1 ± 0.1 and 2.5 ± 0.1 respectively for the AG01522B and patient-derived GBM stem cells for X-ray irradiation using our hypoxia chambers.
Conclusion: We demonstrated the design and application of portable hypoxia chambers for studying cellular radiobiological endpoints after exposure to laser-driven protons at ultra-high dose, conventional protons and X-rays. Suitable levels of reduced oxygen concentration could be maintained in the absence of external gassing to quantify hypoxic effects. The data obtained provided indication of an enhanced residual DNA DSB damage under hypoxic conditions at ultra-high dose rate compared to the conventional protons or X-rays.
(© 2022. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje