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Ruan JL, Lee C, Wouters S, et al. Irradiation at Ultra-High (FLASH) Dose Rates Reduces Acute Normal Tissue Toxicity in the Mouse Gastrointestinal System. Int J Radiat Oncol Biol Phys. 2021;111(5):1250-1261doi: 10.1016/j.ijrobp.2021.08.004.
Ruan, J. L., Lee, C., Wouters, S., Tullis, I. D. C., Verslegers, M., Mysara, M., Then, C. K., Smart, S. C., Hill, M. A., Muschel, R. J., Giaccia, A. J., Vojnovic, B., Kiltie, A. E., & Petersson, K. (2021). Irradiation at Ultra-High (FLASH) Dose Rates Reduces Acute Normal Tissue Toxicity in the Mouse Gastrointestinal System. International journal of radiation oncology, biology, physics, 111(5), 1250-1261. https://doi.org/10.1016/j.ijrobp.2021.08.004
Ruan, Jia-Ling, et al. "Irradiation at Ultra-High (FLASH) Dose Rates Reduces Acute Normal Tissue Toxicity in the Mouse Gastrointestinal System." International journal of radiation oncology, biology, physics vol. 111,5 (2021): 1250-1261. doi: https://doi.org/10.1016/j.ijrobp.2021.08.004
Ruan JL, Lee C, Wouters S, Tullis IDC, Verslegers M, Mysara M, Then CK, Smart SC, Hill MA, Muschel RJ, Giaccia AJ, Vojnovic B, Kiltie AE, Petersson K. Irradiation at Ultra-High (FLASH) Dose Rates Reduces Acute Normal Tissue Toxicity in the Mouse Gastrointestinal System. Int J Radiat Oncol Biol Phys. 2021 Dec 01;111(5):1250-1261. doi: 10.1016/j.ijrobp.2021.08.004. Epub 2021 Aug 14. PMID: 34400268; PMCID: PMC7612009.
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Int J Radiat Oncol Biol Phys. 2021 Dec 01;111(5):1250-1261. doi: 10.1016/j.ijrobp.2021.08.004. Epub 2021 Aug 14.

Irradiation at Ultra-High (FLASH) Dose Rates Reduces Acute Normal Tissue Toxicity in the Mouse Gastrointestinal System.

International journal of radiation oncology, biology, physics

Jia-Ling Ruan, Carl Lee, Shari Wouters, Iain D C Tullis, Mieke Verslegers, Mohamed Mysara, Chee Kin Then, Sean C Smart, Mark A Hill, Ruth J Muschel, Amato J Giaccia, Borivoj Vojnovic, Anne E Kiltie, Kristoffer Petersson

Affiliations

  1. MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, United Kingdom.
  2. Kennedy Institute of Rheumatology, Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Science, University of Oxford, Oxford, United Kingdom.
  3. Interdisciplinary Biosciences Group, Belgian Nuclear Research Center (SCK CEN), Mol, Belgium; Molecular Pathology Group, Cell Biology and Histology and Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, Campus Drie Eiken, University of Antwerp, Antwerp, Belgium.
  4. Interdisciplinary Biosciences Group, Belgian Nuclear Research Center (SCK CEN), Mol, Belgium.
  5. MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, United Kingdom; Radiation Physics, Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund, Sweden. Electronic address: [email protected].

PMID: 34400268 PMCID: PMC7612009 DOI: 10.1016/j.ijrobp.2021.08.004

Abstract

PURPOSE: Preclinical studies using ultra-high dose rate (FLASH) irradiation have demonstrated reduced normal tissue toxicity compared with conventional dose rate (CONV) irradiation, although this finding is not universal. We investigated the effect of temporal pulse structure and average dose rate of FLASH compared with CONV irradiation on acute intestinal toxicity.

MATERIALS AND METHODS: Whole abdomens of C3H mice were irradiated with a single fraction to various doses, using a 6 MeV electron linear accelerator with single pulse FLASH (dose rate = 2-6 × 10

RESULTS: We found statistically significant improvements in crypt survival for mice irradiated with FLASH at doses between 7.5 and 12.5 Gy, with a dose modifying factor of 1.1 for FLASH (7.5 Gy, P < .01; 10 Gy, P < .05; 12.5 Gy, P < .01). This sparing effect was lost when the delivery time was increased, either by increasing the number of irradiation pulses or by prolonging the time between 2 successive pulses. Sparing was observed for average dose rates of ≥280 Gy/s. Fecal microbiome analysis showed that FLASH irradiation caused fewer changes to the microbiota than CONV irradiation.

CONCLUSIONS: This study demonstrates that FLASH irradiation can spare mouse small intestinal crypts and reduce changes in gut microbiome composition compared with CONV irradiation. The higher the average dose rate, the larger the FLASH effect, which is also influenced by temporal pulse structure of the delivery.

Copyright © 2021 Elsevier Inc. All rights reserved.

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