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

Authors :
Songji Zhao
Wenwen Yu
Naoyuki Ukon
Chengbo Tan
Ken-ichi Nishijima
Yoichi Shimizu
Kei Higashikawa
Tohru Shiga
Hiroko Yamashita
Nagara Tamaki
Yuji Kuge
Source :
EJNMMI Research, Vol 9, Iss 1, Pp 1-10 (2019)
Publication Year :
2019
Publisher :
SpringerOpen, 2019.

Abstract

Abstract 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. 18F-Fluoromisonidazole (18F-FMISO) is the most widely used PET probe for imaging tumor hypoxia. In this study, we utilized 18F-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 18F-FMISO and pimonidazole (hypoxia marker for immunohistochemistry), and intertumoral 18F-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 18F-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 18F-FMISO distribution in the tumor was decreased after the eribulin treatment. Conclusions Using 18F-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 18F-FMISO may provide the possibility to detect the early treatment response in clinical patients undergoing eribulin treatment.

Details

Language :
English
ISSN :
2191219X
Volume :
9
Issue :
1
Database :
Directory of Open Access Journals
Journal :
EJNMMI Research
Publication Type :
Academic Journal
Accession number :
edsdoj.b74e7ab1c0f64512b58ee9c9b4135a0b
Document Type :
article
Full Text :
https://doi.org/10.1186/s13550-019-0521-x