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

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. Fu...

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Autores principales: Chaudhary, Pankaj, Gwynne, Deborah C., Odlozilik, Boris, McMurray, Aaron, Milluzzo, Giuliana, Maiorino, Carla, Doria, Domenico, Ahmed, Hamad, Romagnani, Lorenzo, Alejo, Aaron, Padda, Hersimerjit, Green, James, Carroll, David, Booth, Nicola, McKenna, Paul, Kar, Satyabrata, Petringa, Giada, Catalano, Roberto, Cammarata, Francesco P., Cirrone, Giuseppe A. P., McMahon, Stephen J., Prise, Kevin M., Borghesi, Marco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9013042/
https://www.ncbi.nlm.nih.gov/pubmed/35428301
http://dx.doi.org/10.1186/s13014-022-02024-3
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author Chaudhary, Pankaj
Gwynne, Deborah C.
Odlozilik, Boris
McMurray, Aaron
Milluzzo, Giuliana
Maiorino, Carla
Doria, Domenico
Ahmed, Hamad
Romagnani, Lorenzo
Alejo, Aaron
Padda, Hersimerjit
Green, James
Carroll, David
Booth, Nicola
McKenna, Paul
Kar, Satyabrata
Petringa, Giada
Catalano, Roberto
Cammarata, Francesco P.
Cirrone, Giuseppe A. P.
McMahon, Stephen J.
Prise, Kevin M.
Borghesi, Marco
author_facet Chaudhary, Pankaj
Gwynne, Deborah C.
Odlozilik, Boris
McMurray, Aaron
Milluzzo, Giuliana
Maiorino, Carla
Doria, Domenico
Ahmed, Hamad
Romagnani, Lorenzo
Alejo, Aaron
Padda, Hersimerjit
Green, James
Carroll, David
Booth, Nicola
McKenna, Paul
Kar, Satyabrata
Petringa, Giada
Catalano, Roberto
Cammarata, Francesco P.
Cirrone, Giuseppe A. P.
McMahon, Stephen J.
Prise, Kevin M.
Borghesi, Marco
author_sort Chaudhary, Pankaj
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13014-022-02024-3.
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spelling pubmed-90130422022-04-17 Development of a portable hypoxia chamber for ultra-high dose rate laser-driven proton radiobiology applications Chaudhary, Pankaj Gwynne, Deborah C. Odlozilik, Boris McMurray, Aaron Milluzzo, Giuliana Maiorino, Carla Doria, Domenico Ahmed, Hamad Romagnani, Lorenzo Alejo, Aaron Padda, Hersimerjit Green, James Carroll, David Booth, Nicola McKenna, Paul Kar, Satyabrata Petringa, Giada Catalano, Roberto Cammarata, Francesco P. Cirrone, Giuseppe A. P. McMahon, Stephen J. Prise, Kevin M. Borghesi, Marco Radiat Oncol Research 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13014-022-02024-3. BioMed Central 2022-04-15 /pmc/articles/PMC9013042/ /pubmed/35428301 http://dx.doi.org/10.1186/s13014-022-02024-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Chaudhary, Pankaj
Gwynne, Deborah C.
Odlozilik, Boris
McMurray, Aaron
Milluzzo, Giuliana
Maiorino, Carla
Doria, Domenico
Ahmed, Hamad
Romagnani, Lorenzo
Alejo, Aaron
Padda, Hersimerjit
Green, James
Carroll, David
Booth, Nicola
McKenna, Paul
Kar, Satyabrata
Petringa, Giada
Catalano, Roberto
Cammarata, Francesco P.
Cirrone, Giuseppe A. P.
McMahon, Stephen J.
Prise, Kevin M.
Borghesi, Marco
Development of a portable hypoxia chamber for ultra-high dose rate laser-driven proton radiobiology applications
title Development of a portable hypoxia chamber for ultra-high dose rate laser-driven proton radiobiology applications
title_full Development of a portable hypoxia chamber for ultra-high dose rate laser-driven proton radiobiology applications
title_fullStr Development of a portable hypoxia chamber for ultra-high dose rate laser-driven proton radiobiology applications
title_full_unstemmed Development of a portable hypoxia chamber for ultra-high dose rate laser-driven proton radiobiology applications
title_short Development of a portable hypoxia chamber for ultra-high dose rate laser-driven proton radiobiology applications
title_sort development of a portable hypoxia chamber for ultra-high dose rate laser-driven proton radiobiology applications
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9013042/
https://www.ncbi.nlm.nih.gov/pubmed/35428301
http://dx.doi.org/10.1186/s13014-022-02024-3
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