ArticleInternational journal of radiation oncology, biology, physics2026
Timescale of FLASH Sparing Effect Determined by Varying Temporal Split of Dose Delivery in Mice.
Article in International journal of radiation oncology, biology, physics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- FLASH radiotherapy: physico-chemical considerations on ionisation tracks, radical reactions, and the role of oxygen.Radiation oncology (London, England) · 2026Review
- Harnessing the sparing effect of FLASH-RT: From phenomenon observation, radiophysical determinants to molecular mechanisms and synergistic strategies.Materials today. Bio · 2026Review
- Article
- Conditional sparing in FLASH radiotherapy: Conformal dosimetry and ALARA remain essential.Journal of applied clinical medical physics · 2026Review
- Systematic tissue oxygen variation shows the modulation of murine skin radiation toxicity at ultra-high dose rates.Physics in medicine and biology · 2026Article
- Factors Influencing the Biological Effects of FLASH Irradiation.Antioxidants (Basel, Switzerland) · 2025Review
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
purposeTo determine the timescale for ultra high dose rate (UHDR) radiation delivery that dictates FLASH normal tissue sparing and elucidate its relationship to in vivo oxygen dynamics. A split-dose experiment was used to determine the transition time below which the observation of the FLASH sparing effect is preserved. METHODS AND MATERIALS: A 25 Gy dose was split into 2 deliveries (12.5 Gy), with varied interruption times. Albino B6 mice received flank skin irradiation in 8 groups: single-beam UHDR (25 Gy at 415 Gy/s), single-beam conventional dose rate (CDR) (25 Gy at 0.15 Gy/s), or split-beam delivery with 2 lower-dose UHDR beams (12.5 Gy at 415 Gy/s) separated by 0.1, 1, 5, 15, 25, or 120 seconds. Skin damage was scored daily for 31 days, with mixed-effects analysis comparing damage progression across cohorts. Real-time tissue pO
resultsSingle-beam UHDR significantly spared skin versus CDR. In split-dose groups, this sparing effect showed a transition at longer interbeam intervals. Damage progression remained significantly lower than CDR and comparable to single-beam UHDR (P > 0.16) for interruptions <15 seconds. Longer intervals progressively lost tissue sparing. Oximetry indicated an average tissue reoxygenation lifetime of 7.7 ± 1.1 seconds. At the delivery of the second beam, pO
conclusionsObservation of the FLASH sparing effect requires delivery within a critical temporal window that is similar to the timescale of tissue reoxygenation kinetics. The transition time for loss of the FLASH sparing effect in skin roughly corresponds to a diffusion timescale for oxygen, from capillaries to the cells. Although not conclusively demonstrating a mechanism, this unique finding supports the likelihood that local oxygen depletion or consumption underlies the FLASH tissue sparing effect observed in vivo, with important implications for clinical implementation and the timescale needed for multibeam FLASH radiation therapy.
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