Noninvasive small-animal imaging of galectin-1 upregulation for predicting tumor resistance to radiotherapy

Publication date: March 2018
Source:Biomaterials, Volume 158
Author(s): Jianhao Lai, Dehua Lu, Chenran Zhang, Hua Zhu, Liquan Gao, Yanpu Wang, Rui Bao, Yang Zhao, Bing Jia, Fan Wang, Zhi Yang, Zhaofei Liu
Increasing evidence indicates that the overexpression of galectin-1, a member of the galectin family, is related to tumor progression and invasion, as well as tumor resistance to therapies (e.g., radiotherapy). Herein, we investigated whether near-infrared fluorescence (NIRF) imaging and positron-emission tomography (PET) were sensitive approaches for detecting and quantitating galectin-1 upregulation in vivo. An anti-galectin-1 antibody was labeled with either an NIRF dye or ⁶⁴Cu, and NIRF and PET imaging using the resulting probes (Dye-αGal-1 and ⁶⁴Cu- 1,4,7-triazacyclononane-1,4,7-triacetic acid [NOTA]-αGal-1) were performed in 4T1 breast cancer-bearing mice treated with several rounds of sorafenib. Radiotherapy was performed in vitro and in vivo to identify the role of galectin-1 in radioresistance. NIRF and PET imaging both revealed significantly increased upregulation of galectin-1 in the hypoxic tumors after sorafenib treatment, which was verified by ex vivo biodistribution, western blotting, and enzyme-linked immunosorbent assays. Galectin-1 specific inhibition by thiodigalactoside dramatically improved the efficacy of radiotherapy, and overcame sorafenib-induced radiotherapy resistance. Taken together, galectin-1 is a key mediator of tumor resistance to radiotherapy. Targeted molecular imaging allows for real-time, noninvasive, and quantitative detection of the dynamic changes in galectin-1 levels in vivo; this introduces the possibility of early detection of tumor resistance to therapies.

Graphical abstract

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