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

Bo, Tomoki; Yasui, Hironobu; Shiga, Tohru; Shibata, Yuki; Fujimoto, Masaki; Suzuki, Motofumi; Higashikawa, Kei; Miyamoto, Naoki; Inanami, Osamu; Kuge, Yuji

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

Bo, Tomoki; Yasui, Hironobu; Shiga, Tohru et al.

European Journal of Nuclear Medicine and Molecular Imaging, 2021, 49(3), 821-833

Permalink : https://hdl.handle.net/2115/86668

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アクセス権	open access
URI	https://hdl.handle.net/2115/86668
タイトル	Eribulin improves tumor oxygenation demonstrated by F-18-DiFA hypoxia imaging, leading to radio-sensitization in human cancer xenograft models
著者	Bo, Tomoki ; Yasui, Hironobu ; Shiga, Tohru ; Shibata, Yuki ; Fujimoto, Masaki ; Suzuki, Motofumi ; Higashikawa, Kei ; Miyamoto, Naoki ; Inanami, Osamu ; Kuge, Yuji
e-Rad_Researcher 90878141 著者名 Bo, Tomoki
e-Rad_Researcher 10570228 著者名 Yasui, Hironobu
e-Rad_Researcher 80374495 著者名 Shiga, Tohru
著者名 Shibata, Yuki
著者名 Fujimoto, Masaki
著者名 Suzuki, Motofumi
e-Rad_Researcher 10756878 著者名 Higashikawa, Kei
e-Rad_Researcher 00552879 著者名 Miyamoto, Naoki
e-Rad_Researcher 10193559 著者名 Inanami, Osamu
e-Rad_Researcher 70321958 著者名 Kuge, Yuji
言語	英語
キーワード	Eribulin
	F-18-DiFA
	Hypoxia
	Radiation
	PET
	CT imaging
発行日	2021-09-01
出版者	Springer
収録物名	European Journal of Nuclear Medicine and Molecular Imaging
巻(号)	49(3)
ページ	821-833
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	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: http://dx.doi.org/10.1007/s00259-021-05544-4
PISSN	1619-7070
EISSN	1619-7089
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1007/s00259-021-05544-4