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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.

Keywords: (64)Cu; Galectin-1; Hypoxia; ImmunoPET; Radiotherapy.

The metastatic spread of primary tumors to regional lymph nodes (LNs) is an important prognostic indicator for cancer staging and clinical therapy. Therefore, developing lymphatic mapping probes with improved accuracy and efficiency is of vital importance. Conjugated polymers (CPs) have been established as useful optical probes for sensitive biological and chemical detection. As a member of CPs family, polythiophene derivatives have drawn increasing attraction because of their superior photostability, signal amplification ability, and flexible structures for modification. In addition, these excellent properties allow the promising in vivo application to real-time LNs mapping. Here, we first reported a radiolabeled dual-modal probe based on the polythiophene derivative (99mTc-PTP) that was used for LNs mapping with high sensitivity and specificity by preoperative single-photon emission computed tomography imaging and intraoperative optical guidance. 99mTc-PTP exhibits an excellent radio-fluorescence guidance ability and a remarkable biocompatibility and holds great potential to be a powerful probe for noninvasive LNs mapping.

Keywords: SPECT imaging; dual modality; lymph nodes mapping; optical imaging; polythiophene.