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Background  Eribulin, an inhibitor of microtubule dynamics, shows antitumor potency against a variety of solid cancers through its antivascular activity and remodeling of tumor vasculature.  18 F-Fluoromisonidazole ( 18 F-FMISO) is the most widely used PET probe for imaging tumor hypoxia. In this study, we utilized  18 F-FMISO to clarify the effects of eribulin on the tumor hypoxic condition in comparison with histological findings.    Material and methods  Mice bearing a human cancer cell xenograft were intraperitoneally administered a single dose of eribulin (0.3 or 1.0 mg/kg) or saline. Three days after the treatment, mice were injected with  18 F-FMISO and pimonidazole (hypoxia marker for immunohistochemistry), and intertumoral  18 F-FMISO accumulation levels and histological characteristics were determined. PET/CT was performed pre- and post-treatment with eribulin (0.3 mg/kg, i.p.).    Results  The  18 F-FMISO accumulation levels and percent pimonidazole-positive hypoxic area were significantly lower, whereas the number of microvessels was higher in the tumors treated with eribulin. The PET/CT confirmed that  18 F-FMISO distribution in the tumor was decreased after the eribulin treatment.    Conclusions  Using  18 F-FMISO, we demonstrated the elimination of the tumor hypoxic condition by eribulin treatment, concomitantly with the increase in microvessel density. These findings indicate that PET imaging using  18 F-FMISO may provide the possibility to detect the early treatment response in clinical patients undergoing eribulin treatment.

Elimination of tumor hypoxia by eribulin demonstrated by 18F-FMISO hypoxia imaging in human tumor xenograft models