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Investigating the FLASH Effect in a Rat Brain Organotypic Model With a Novel High-Energy Electron Beam.

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Title: Investigating the FLASH Effect in a Rat Brain Organotypic Model With a Novel High-Energy Electron Beam.
Authors: Kay, Tyler V.1 (AUTHOR), Price, Anna L.1 (AUTHOR), Sprenger, Markus1 (AUTHOR), Radosova, Victoria J.P.1 (AUTHOR), Thompson, Andrew1 (AUTHOR), Martin, Eric L.2,3 (AUTHOR), Dunn, Denise1 (AUTHOR), Popov, Victor2,3 (AUTHOR), Mikhailov, Stepan2,3 (AUTHOR), Reitman, Zachary J.1 (AUTHOR), Wu, Ying K.2,3 (AUTHOR), Floyd, Scott R.1 (AUTHOR) scott.floyd@duke.edu, Oldham, Mark1 (AUTHOR) mark.oldham@duke.edu
Source: International Journal of Radiation Oncology, Biology, Physics. Mar2026, Vol. 124 Issue 3, p759-764. 6p.
Subjects: Electron beams, Microglia, Cytokines, Cancer treatment, Radiotherapy, Cancer cell growth, Brain metastasis
Abstract: Ultrahigh dose rate (FLASH) radiation therapy is reported to reduce normal tissue toxicity while maintaining tumor control; however, mechanism(s) remain obscure. To study FLASH mechanisms in brain tissue, we developed a novel experimental platform featuring a specialized high-energy electron linear accelerator, High Intensity Gamma Ray Source (HIGS), paired with an organotypic ex vivo brain metastasis model. We varied interpulse spacing to modulate the mean dose rate (MDR) of our unique 35 MeV electron beam, while maintaining extremely high instantaneous dose rate (IDR). We characterized dosimetry and targeting accuracy of the FLASH beam with film dosimetry. We combined this FLASH beam with an organotypic rat brain slice/breast carcinoma coculture model of brain metastasis to assess effects on normal and neoplastic tissues. Live-cell and bioluminescence imaging demonstrated cancer cell growth effects, whereas normal tissue responses and immune activation were assessed using live-cell imaging, cytokine profiles, and confocal microscopy. We performed comparison experiments with 20 MeV electrons from a Varian clinical linear accelerator (VCLA) using conventional dose rates. The highest IDR of the FLASH beam to date was 20.7 ± 0.6 MGy/s, with maximum MDR of 20.7 MGy/s delivered in 1 pulse of 1 µs duration. Beam targeting was accurate to <1 mm and reproducible. HIGS-FLASH and VCLA dose rates equivalently decreased cancer cell growth. HIGS-FLASH irradiation significantly increased tumor necrosis factor α and fractalkine levels and confocal microscopy revealed distinct changes in microglial morphology slices suggesting microglia activation. Our novel experimental platform produces extremely high dose rates and rapid normal/neoplastic tissue readouts for mechanistic research into the effects of FLASH radiation in the brain. HIGS-FLASH irradiation induces comparable cancer cell growth inhibition but differential effects on cytokines and microglial morphology, suggesting that acute innate immune responses may be involved in FLASH normal tissue effects in the brain. [ABSTRACT FROM AUTHOR]
Copyright of International Journal of Radiation Oncology, Biology, Physics is the property of Pergamon Press - An Imprint of Elsevier Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Engineering Source
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DbLabel: Engineering Source
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  Data: Investigating the FLASH Effect in a Rat Brain Organotypic Model With a Novel High-Energy Electron Beam.
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  Data: Ultrahigh dose rate (FLASH) radiation therapy is reported to reduce normal tissue toxicity while maintaining tumor control; however, mechanism(s) remain obscure. To study FLASH mechanisms in brain tissue, we developed a novel experimental platform featuring a specialized high-energy electron linear accelerator, High Intensity Gamma Ray Source (HIGS), paired with an organotypic ex vivo brain metastasis model. We varied interpulse spacing to modulate the mean dose rate (MDR) of our unique 35 MeV electron beam, while maintaining extremely high instantaneous dose rate (IDR). We characterized dosimetry and targeting accuracy of the FLASH beam with film dosimetry. We combined this FLASH beam with an organotypic rat brain slice/breast carcinoma coculture model of brain metastasis to assess effects on normal and neoplastic tissues. Live-cell and bioluminescence imaging demonstrated cancer cell growth effects, whereas normal tissue responses and immune activation were assessed using live-cell imaging, cytokine profiles, and confocal microscopy. We performed comparison experiments with 20 MeV electrons from a Varian clinical linear accelerator (VCLA) using conventional dose rates. The highest IDR of the FLASH beam to date was 20.7 &#177; 0.6 MGy/s, with maximum MDR of 20.7 MGy/s delivered in 1 pulse of 1 &#181;s duration. Beam targeting was accurate to &lt;1 mm and reproducible. HIGS-FLASH and VCLA dose rates equivalently decreased cancer cell growth. HIGS-FLASH irradiation significantly increased tumor necrosis factor α and fractalkine levels and confocal microscopy revealed distinct changes in microglial morphology slices suggesting microglia activation. Our novel experimental platform produces extremely high dose rates and rapid normal/neoplastic tissue readouts for mechanistic research into the effects of FLASH radiation in the brain. HIGS-FLASH irradiation induces comparable cancer cell growth inhibition but differential effects on cytokines and microglial morphology, suggesting that acute innate immune responses may be involved in FLASH normal tissue effects in the brain. [ABSTRACT FROM AUTHOR]
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  Data: &lt;i&gt;Copyright of International Journal of Radiation Oncology, Biology, Physics is the property of Pergamon Press - An Imprint of Elsevier Science and its content may not be copied or emailed to multiple sites without the copyright holder&#39;s express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.&lt;/i&gt; (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=egs&AN=191321743
RecordInfo BibRecord:
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      – Type: doi
        Value: 10.1016/j.ijrobp.2025.09.057
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 6
        StartPage: 759
    Subjects:
      – SubjectFull: Electron beams
        Type: general
      – SubjectFull: Microglia
        Type: general
      – SubjectFull: Cytokines
        Type: general
      – SubjectFull: Cancer treatment
        Type: general
      – SubjectFull: Radiotherapy
        Type: general
      – SubjectFull: Cancer cell growth
        Type: general
      – SubjectFull: Brain metastasis
        Type: general
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      – TitleFull: Investigating the FLASH Effect in a Rat Brain Organotypic Model With a Novel High-Energy Electron Beam.
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            – D: 01
              M: 03
              Text: Mar2026
              Type: published
              Y: 2026
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