Evidence map›Paper›PMID 33845146›Full record

ArticleInternational journal of radiation oncology, biology, physics2021

Quantification of Oxygen Depletion During FLASH Irradiation In Vitro and In Vivo.

Xu Cao, Rongxiao Zhang, Tatiana V Esipova, Srinivasa Rao Allu, Ramish Ashraf, Mahbubur Rahman, Jason R Gunn, Petr Bruza, David J Gladstone, Benjamin B Williams and 4 more

Abstract read
In one paragraph

Article in International journal of radiation oncology, biology, physics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
127citing papers in PubMed, 3 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

127 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
  2. The current status of FLASH particle therapy: a systematic review.Physical and engineering sciences in medicine · 2023
    Pooled it
  3. Pooled it
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Proton FLASH Exposure Preserves Gut Commensal Microbiomes and Spares Intestinal Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article

67 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Xu CaoThayer School of Engineering, Dartmouth College, Hanover, New Hampshire; Engineering Research Center of Molecular and Neuro Imaging of the Ministry of Education & School of Life Science and Technology, Xidian University, Xi'an, Shaanxi, China.
Rongxiao ZhangThayer School of Engineering, Dartmouth College, Hanover, New Hampshire; Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire; Department of Medicine, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire.
Tatiana V EsipovaDepartment of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Chemistry, School or Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania.
Srinivasa Rao AlluDepartment of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Chemistry, School or Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania.
Ramish AshrafThayer School of Engineering, Dartmouth College, Hanover, New Hampshire.
Mahbubur RahmanThayer School of Engineering, Dartmouth College, Hanover, New Hampshire.
Jason R GunnThayer School of Engineering, Dartmouth College, Hanover, New Hampshire.
Petr BruzaThayer School of Engineering, Dartmouth College, Hanover, New Hampshire.
David J GladstoneThayer School of Engineering, Dartmouth College, Hanover, New Hampshire; Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire; Department of Medicine, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire.
Benjamin B WilliamsThayer School of Engineering, Dartmouth College, Hanover, New Hampshire; Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire; Department of Medicine, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire.
Harold M SwartzThayer School of Engineering, Dartmouth College, Hanover, New Hampshire; Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire; Department of Medicine, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire.
P Jack HoopesThayer School of Engineering, Dartmouth College, Hanover, New Hampshire; Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire; Department of Surgery, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire.
Sergei A VinogradovDepartment of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Chemistry, School or Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: vinograd.upenn@gmail.com.
Brian W PogueThayer School of Engineering, Dartmouth College, Hanover, New Hampshire; Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire; Department of Surgery, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire. Electronic address: brian.w.pogue@dartmouth.edu.

Funding

Translational Engineering in Cancer (TEC)P30CA023108 · NCI · DARTMOUTH COLLEGE · PI Steven D Leach · 1985 to 2026
$91.3M
Cerenkov excited luminescence sheet imaging (CELSI)R01EB024498 · NIBIB · DARTMOUTH COLLEGE · PI POGUE, BRIAN WILLIAM · 2017 to 2020
$2.2M
Oxygen imaging by phosphorescence quenchingU24EB028941 · NIBIB · UNIVERSITY OF PENNSYLVANIA · PI VINOGRADOV, SERGEI · 2019 to 2023
$1.6M
A molecular probe for high-resolution dual imaging of temperature and oxygen in vivoR21EB027397 · NIBIB · UNIVERSITY OF PENNSYLVANIA · PI VINOGRADOV, SERGEI · 2018 to 2019
$464k
NCI NIH HHS P30 CA023108NIBIB NIH HHS R01 EB024498NIBIB NIH HHS R21 EB027397NIBIB NIH HHS U24 EB028941
6 · The paper itself

Abstract

purposeDelivery of radiation at ultrahigh dose rates (UHDRs), known as FLASH, has recently been shown to preferentially spare normal tissues from radiation damage compared with tumor tissues. However, the underlying mechanism of this phenomenon remains unknown, with one of the most widely considered hypotheses being that the effect is related to substantial oxygen depletion upon FLASH, thereby altering the radiochemical damage during irradiation, leading to different radiation responses of normal and tumor cells. Testing of this hypothesis would be advanced by direct measurement of tissue oxygen in vivo during and after FLASH irradiation. METHODS AND MATERIALS: Oxygen measurements were performed in vitro and in vivo using the phosphorescence quenching method and a water-soluble molecular probe Oxyphor 2P. The changes in oxygen per unit dose (G-values) were quantified in response to irradiation by 10 MeV electron beam at either UHDR reaching 300 Gy/s or conventional radiation therapy dose rates of 0.1 Gy/s.

resultsIn vitro experiments with 5% bovine serum albumin solutions at 23°C resulted in G-values for oxygen consumption of 0.19 to 0.21 mm Hg/Gy (0.34-0.37 μM/Gy) for conventional irradiation and 0.16 to 0.17 mm Hg/Gy (0.28-0.30 μM/Gy) for UHDR irradiation. In vivo, the total decrease in oxygen after a single fraction of 20 Gy FLASH irradiation was 2.3 ± 0.3 mm Hg in normal tissue and 1.0 ± 0.2 mm Hg in tumor tissue (P < .00001), whereas no decrease in oxygen was observed from a single fraction of 20 Gy applied in conventional mode.

conclusionsOur observations suggest that oxygen depletion to radiologically relevant levels of hypoxia is unlikely to occur in bulk tissue under FLASH irradiation. For the same dose, FLASH irradiation induces less oxygen consumption than conventional irradiation in vitro, which may be related to the FLASH sparing effect. However, the difference in oxygen depletion between FLASH and conventional irradiation could not be quantified in vivo because measurements of oxygen depletion under conventional irradiation are hampered by resupply of oxygen from the blood.

Indexed as

AnimalsMiceNeoplasms, ExperimentalOxygenOxygen ConsumptionRadiotherapy DosageOxygen

Identifiers

PMID33845146
PMCPMC8338745

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.