In vivo measurements of change in tissue oxygen level during irradiation reveal novel dose rate dependence.

Journal

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
ISSN: 1879-0887
Titre abrégé: Radiother Oncol
Pays: Ireland
ID NLM: 8407192

Informations de publication

Date de publication:
17 Sep 2024
Historique:
received: 13 05 2024
revised: 09 09 2024
accepted: 12 09 2024
medline: 20 9 2024
pubmed: 20 9 2024
entrez: 19 9 2024
Statut: aheadofprint

Résumé

This study aimed to investigate the radiochemical oxygen depletion (ROD) in vivo by directly measuring oxygen levels in various mouse tissues during ultra-high dose rate (UHDR) irradiation at clinically relevant doses and dose rates. Mice bearing subcutaneous human glioblastoma (U-87 MG) tumors were used for tumor and normal tissue (skin, muscle, brain) measurements. An oxygen-sensitive phosphorescent probe (Oxyphor PtG4) was injected into the tissues, and oxygen levels were monitored using a fiberoptic phosphorometer during UHDR irradiation with a 6 MeV electron linear accelerator (LINAC). Dose escalation experiments (10-40 Gy) were performed at a dose rate of 1300 Gy/s, and dose rate escalation experiments were conducted at a fixed dose of 40 Gy with dose rates ranging from 2 to 101 Gy/s. Radiation-induced change in tissue oxygenation (ΔpO While UHDR irradiation induces measurable oxygen depletion in tissues, the observed changes in oxygenation levels do not support the hypothesis that ROD-induced radioresistance is responsible for the FLASH tissue-sparing effect at clinically relevant doses and dose rates. These findings highlight the need for further investigation into alternative mechanisms underlying the FLASH effect.

Sections du résumé

BACKGROUND AND PURPOSE OBJECTIVE
This study aimed to investigate the radiochemical oxygen depletion (ROD) in vivo by directly measuring oxygen levels in various mouse tissues during ultra-high dose rate (UHDR) irradiation at clinically relevant doses and dose rates.
MATERIALS AND METHODS METHODS
Mice bearing subcutaneous human glioblastoma (U-87 MG) tumors were used for tumor and normal tissue (skin, muscle, brain) measurements. An oxygen-sensitive phosphorescent probe (Oxyphor PtG4) was injected into the tissues, and oxygen levels were monitored using a fiberoptic phosphorometer during UHDR irradiation with a 6 MeV electron linear accelerator (LINAC). Dose escalation experiments (10-40 Gy) were performed at a dose rate of 1300 Gy/s, and dose rate escalation experiments were conducted at a fixed dose of 40 Gy with dose rates ranging from 2 to 101 Gy/s.
RESULTS RESULTS
Radiation-induced change in tissue oxygenation (ΔpO
CONCLUSION CONCLUSIONS
While UHDR irradiation induces measurable oxygen depletion in tissues, the observed changes in oxygenation levels do not support the hypothesis that ROD-induced radioresistance is responsible for the FLASH tissue-sparing effect at clinically relevant doses and dose rates. These findings highlight the need for further investigation into alternative mechanisms underlying the FLASH effect.

Identifiants

DOI: 10.1016/j.radonc.2024.110539 PMID: 39299575
pubmed: 39299575
pii: S0167-8140(24)03517-5
doi: 10.1016/j.radonc.2024.110539
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

110539

Informations de copyright

Copyright © 2024. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marie-Catherine Vozenin reports financial support was provided by Swiss National Science Foundation. Marie-Catherine Vozenin reports financial support was provided by National Institutes of Health. Mirna El Khatib reports financial support was provided by National Institutes of Health. Paola Ballesteros-Zebadua reports financial support was provided by Swiss National Science Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Veljko Grilj (V)

Institute of Radiation Physics, University Hospital and University of Lausanne, Lausanne, Switzerland; Radiation Oncology Laboratory, Department of Radiation Oncology, Lausanne, University Hospital and University of Lausanne, Lausanne, Switzerland. Electronic address: Veljko.Grilj@chuv.ch.

Ron J Leavitt (RJ)

Radiation Oncology Laboratory, Department of Radiation Oncology, Lausanne, University Hospital and University of Lausanne, Lausanne, Switzerland.

Mirna El Khatib (M)

Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States; Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, United States.

Ryan Paisley (R)

Institute of Radiation Physics, University Hospital and University of Lausanne, Lausanne, Switzerland.

Javier Franco-Perez (J)

Radiation Oncology Laboratory, Department of Radiation Oncology, Lausanne, University Hospital and University of Lausanne, Lausanne, Switzerland; Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suarez, Mexico City, Mexico; LiRR- Laboratory of Innovation in Radiobiology Applied to Radiotherapy, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

Benoit Petit (B)

Radiation Oncology Laboratory, Department of Radiation Oncology, Lausanne, University Hospital and University of Lausanne, Lausanne, Switzerland; Radiotherapy and Radiobiology Sector, Radiation Therapy Service, University Hospital of Geneva, Geneva, Switzerland; LiRR- Laboratory of Innovation in Radiobiology Applied to Radiotherapy, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

Paola Ballesteros-Zebadua (P)

Radiation Oncology Laboratory, Department of Radiation Oncology, Lausanne, University Hospital and University of Lausanne, Lausanne, Switzerland; Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suarez, Mexico City, Mexico; LiRR- Laboratory of Innovation in Radiobiology Applied to Radiotherapy, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

Marie-Catherine Vozenin (MC)

Radiation Oncology Laboratory, Department of Radiation Oncology, Lausanne, University Hospital and University of Lausanne, Lausanne, Switzerland; Radiotherapy and Radiobiology Sector, Radiation Therapy Service, University Hospital of Geneva, Geneva, Switzerland; LiRR- Laboratory of Innovation in Radiobiology Applied to Radiotherapy, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

Classifications MeSH