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The FLASH effect depends on oxygen concentration

Adrian, Gabriel LU orcid ; Konradsson, Elise LU ; Lempart, Michael ; Bäck, Sven LU ; Ceberg, Crister LU orcid and Petersson, Kristoffer LU (2019) In British Journal of Radiology 93(1106).
Abstract

OBJECTIVE: Recent in vivo results have shown prominent tissue sparing effect of radiotherapy with ultra-high dose rates (FLASH) compared to conventional dose rates (CONV). Oxygen depletion has been proposed as the underlying mechanism, but in vitro data to support this have been lacking. The aim of the current study was to compare FLASH to CONV irradiation under different oxygen concentrations in vitro. METHODS: Prostate cancer cells were irradiated at different oxygen concentrations (relative partial pressure ranging between 1.6 and 20%) with a 10 MeV electron beam at a dose rate of either 600 Gy/s (FLASH) or 14 Gy/min (CONV), using a modified clinical linear accelerator. We evaluated the surviving fraction of cells using clonogenic... (More)

OBJECTIVE: Recent in vivo results have shown prominent tissue sparing effect of radiotherapy with ultra-high dose rates (FLASH) compared to conventional dose rates (CONV). Oxygen depletion has been proposed as the underlying mechanism, but in vitro data to support this have been lacking. The aim of the current study was to compare FLASH to CONV irradiation under different oxygen concentrations in vitro. METHODS: Prostate cancer cells were irradiated at different oxygen concentrations (relative partial pressure ranging between 1.6 and 20%) with a 10 MeV electron beam at a dose rate of either 600 Gy/s (FLASH) or 14 Gy/min (CONV), using a modified clinical linear accelerator. We evaluated the surviving fraction of cells using clonogenic assays after irradiation with doses ranging from 0 to 25 Gy. RESULTS: Under normoxic conditions, no differences between FLASH and CONV irradiation were found. For hypoxic cells (1.6%), the radiation response was similar up to a dose of about 5-10 Gy, above which increased survival was shown for FLASH compared to CONV irradiation. The increased survival was shown to be significant at 18 Gy, and the effect was shown to depend on oxygen concentration. CONCLUSION: The in vitro FLASH effect depends on oxygen concentration. Further studies to characterize and optimize the use of FLASH in order to widen the therapeutic window are indicated. ADVANCES IN KNOWLEDGE: This paper shows in vitro evidence for the role of oxygen concentration underlying the difference between FLASH and CONV irradiation.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
British Journal of Radiology
volume
93
issue
1106
article number
20190702
publisher
British Institute of Radiology
external identifiers
  • scopus:85078391658
  • pmid:31825653
ISSN
1748-880X
DOI
10.1259/bjr.20190702
language
English
LU publication?
yes
id
3da282b0-7aca-4033-84c8-54335cfd0231
date added to LUP
2020-02-04 16:46:16
date last changed
2024-04-17 03:42:30
@article{3da282b0-7aca-4033-84c8-54335cfd0231,
  abstract     = {{<p>OBJECTIVE: Recent in vivo results have shown prominent tissue sparing effect of radiotherapy with ultra-high dose rates (FLASH) compared to conventional dose rates (CONV). Oxygen depletion has been proposed as the underlying mechanism, but in vitro data to support this have been lacking. The aim of the current study was to compare FLASH to CONV irradiation under different oxygen concentrations in vitro. METHODS: Prostate cancer cells were irradiated at different oxygen concentrations (relative partial pressure ranging between 1.6 and 20%) with a 10 MeV electron beam at a dose rate of either 600 Gy/s (FLASH) or 14 Gy/min (CONV), using a modified clinical linear accelerator. We evaluated the surviving fraction of cells using clonogenic assays after irradiation with doses ranging from 0 to 25 Gy. RESULTS: Under normoxic conditions, no differences between FLASH and CONV irradiation were found. For hypoxic cells (1.6%), the radiation response was similar up to a dose of about 5-10 Gy, above which increased survival was shown for FLASH compared to CONV irradiation. The increased survival was shown to be significant at 18 Gy, and the effect was shown to depend on oxygen concentration. CONCLUSION: The in vitro FLASH effect depends on oxygen concentration. Further studies to characterize and optimize the use of FLASH in order to widen the therapeutic window are indicated. ADVANCES IN KNOWLEDGE: This paper shows in vitro evidence for the role of oxygen concentration underlying the difference between FLASH and CONV irradiation.</p>}},
  author       = {{Adrian, Gabriel and Konradsson, Elise and Lempart, Michael and Bäck, Sven and Ceberg, Crister and Petersson, Kristoffer}},
  issn         = {{1748-880X}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{1106}},
  publisher    = {{British Institute of Radiology}},
  series       = {{British Journal of Radiology}},
  title        = {{The FLASH effect depends on oxygen concentration}},
  url          = {{http://dx.doi.org/10.1259/bjr.20190702}},
  doi          = {{10.1259/bjr.20190702}},
  volume       = {{93}},
  year         = {{2019}},
}