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Eribulin improves tumor oxygenation demonstrated by F-18-DiFA hypoxia imaging, leading to radio-sensitization in human cancer xenograft models

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Title: Eribulin improves tumor oxygenation demonstrated by F-18-DiFA hypoxia imaging, leading to radio-sensitization in human cancer xenograft models
Authors: Bo, Tomoki Browse this author →KAKEN DB
Yasui, Hironobu Browse this author →KAKEN DB
Shiga, Tohru Browse this author →KAKEN DB
Shibata, Yuki Browse this author
Fujimoto, Masaki Browse this author
Suzuki, Motofumi Browse this author
Higashikawa, Kei Browse this author →KAKEN DB
Miyamoto, Naoki Browse this author →KAKEN DB
Inanami, Osamu Browse this author →KAKEN DB
Kuge, Yuji Browse this author →KAKEN DB
Keywords: Eribulin
CT imaging
Issue Date: 1-Sep-2021
Publisher: Springer
Journal Title: European Journal of Nuclear Medicine and Molecular Imaging
Volume: 49
Issue: 3
Start Page: 821
End Page: 833
Publisher DOI: 10.1007/s00259-021-05544-4
Abstract: Purpose Eribulin, an inhibitor of microtubule dynamics, is known to show antitumor effects through its remodeling activity in the tumor vasculature. However, the extent to which the improvement of tumor hypoxia by eribulin affects radio-sensitivity remains unclear. We utilized 1-(2,2-dihydroxymethyl-3-F-18-fluoropropyl)-2-nitroimidazole (F-18-DiFA), a new PET probe for hypoxia, to investigate the effects of eribulin on tumor hypoxia and evaluate the radio-sensitivity during eribulin treatment. Methods Mice bearing human breast cancer MDA-MB-231 cells or human lung cancer NCI-H1975 cells were administered a single dose of eribulin. After administration, mice were injected with F-18-DiFA and pimonidazole, and tumor hypoxia regions were analyzed. For the group that received combined treatment with radiation, F-18-DiFA PET/CT imaging was performed before tumors were locally X-irradiated. Tumor size was measured every other day after irradiation. Results Eribulin significantly reduced F-18-DiFA accumulation levels in a dose-dependent manner. Furthermore, the reduction in F-18-DiFA accumulation levels by eribulin was most significant 7 days after treatment. These results were also supported by reduction of the pimonidazole-positive hypoxic region. The combined treatment showed significant retardation of tumor growth in comparison with the control, radiation-alone, and drug-alone groups. Importantly, tumor growth after irradiation was inversely correlated with F-18-DiFA accumulation. Conclusion These results demonstrated that F-18-DiFA PET/CT clearly detected eribulin-induced tumor oxygenation and that eribulin efficiently enhanced the antitumor activity of radiation by improving tumor oxygenation.
Rights: This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at:
Type: article (author version)
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 安井 博宣

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