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 over -expressed 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.

Automated summary

Surgical resection is the preferred treatment for colorectal cancer, but effective targeting probes for imaging-guided surgical navigation are lacking. In this study, a fluorescent probe ABT-510 labeled with fluorescein isothiocyanate or near-infrared dye MPA was developed and found to have high selectivity and specificity for cells or tissues with high CD36 expression. The probe showed excellent tumor delineation characteristics and antiangiogenic effects, making it a desirable tool for CRC imaging and surgical navigation.