Development and Evaluation of a Peptide Heterodimeric Tracer Targeting CXCR4 and Integrin α(v)β(3) for Pancreatic Cancer Imaging

Nowadays, pancreatic cancer is still a formidable disease to diagnose. The CXC chemokine receptor 4 (CXCR4) and integrin α(v)β(3) play important roles in tumor development, progression, invasion, and metastasis, which are overexpressed in many types of human cancers. In this study, we developed a heterodimeric tracer (68)Ga-yG5-RGD targeting both CXCR4 and integrin α(v)β(3), and evaluated its feasibility and utility in PET imaging of pancreatic cancer. The (68)Ga-yG5-RGD could accumulate in CXCR4/integrin α(v)β(3) positive BxPC3 tumors in a high concentration and was much higher than that of (68)Ga-yG5 (p < 0.001) and (68)Ga-RGD (p < 0.001). No increased uptake of (68)Ga-yG5-RGD was found in MX-1 tumors (CXCR4/integrin α(v)β(3), negative). In addition, the uptake of (68)Ga-yG5-RGD in BxPC3 was significantly blocked by excess amounts of AMD3100 (an FDA-approved CXCR4 antagonist) and/or unlabeled RGD (p < 0.001), confirming its dual-receptor targeting properties. The ex vivo biodistribution and immunohistochemical results were consistent with the in vivo imaging results. The dual-receptor targeting strategy achieved improved tumor-targeting efficiency and prolonged tumor retention in BxPC3 tumors, suggesting (68)Ga-yG5-RGD is a promising tracer for the noninvasive detection of tumors that express either CXCR4 or integrin α(v)β(3) or both, and therefore may have good prospects for clinical translation.