Integrin α6-Targeted Positron Emission Tomography Imaging of Colorectal Cancer

Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer deaths worldwide. Integrin alpha 6 is overexpressed in all stages of CRC which makes it a potential diagnostic biomarker for CRC. Previously, we identified an integrin alpha 6-targeted peptide CRWYDENAC (dubbed RWY) using phage display technology and employed it for nasopharyngeal carcinoma specific nanotherapeutics. In this study, we developed a radiotracer, F-18-RWY, based on this integrin alpha 6-targeted RWY peptide for positron emission tomography (PET) imaging of CRC. Integrin alpha 6 was overexpressed on several CRC cells including HT29 cells where the biotin-labeled RWY peptide colocalized with integrin alpha 6. F-18-RWY PET imaging was performed on subcutaneous, chemically induced, and genetically engineered CRC mice. 'F-RWY generated high PET signals in subcutaneous HT29 tumors, and the tumor uptake of F-18-RWY was reduced by a blocking study using nonradio-labeled RWY. Moreover, F-18-RWY PET imaging enabled detection of CRC in chemically induced and genetically engineered CRC mice. The overexpression of integrin alpha 6 in tumor tissues isolated from chemically induced and genetically engineered CRC mice was confirmed. These results demonstrate the potential clinical application of F-18-RWY for PET imaging of CRC.