Preclinical Evaluation of CD36-Targeting Antiangiogenic Peptide ABT-510 for Near-Infrared Fluorescence Molecular Imaging of Colorectal Cancer

Surgical resection constitutes the first choice of treatment for colorectal cancer (CRC). Despite advancements in intraoperative navigation, there remains a considerable lack of effective targeting probes for the imaging-guided surgical navigation of CRC owing to their high heterogeneity. Hence, developing a suitable fluorescent probe to detect the specific types of CRC populations is crucial. Herein, we labeled ABT-510, a small, CD36-targeting thrombospondin-1–mimetic peptide overexpressed in various cancer types, with fluorescein isothiocyanate or near-infrared dye MPA. We found that fluorescence-conjugated ABT-510 exhibited excellent selectivity and specificity toward cells or tissues with high CD36 expression. The tumor-to-colorectal signal ratios were 11.28 ± 0.61 (95% confidence interval) and 10.74 ± 0.07 (95% confidence interval) in subcutaneous HCT-116 and HT-29 tumor-bearing nude mice, respectively. Moreover, high signal contrast was observed in the orthotopic and liver metastatic CRC xenograft mouse models. Furthermore, MPA–PEG4–r-ABT-510 exhibited an antiangiogenic effect via tube information assay with human umbilical vein endothelial cells. Overall, MPA–PEG4–r-ABT-510 presents rapid and precise tumor delineation characteristics, thereby making it a desirable tool for CRC imaging and surgical navigation.