Development and Evaluation of a Peptide Heterodimeric Tracer Targeting CXCR4 and Integrin αvβ3 for Pancreatic Cancer Imaging
Yaqun Jiang, Long Yu, Hao Ji, Pengxin Qiao, Qingyao Liu, Xiaotian Xia, Chunxia Qin, Yongxue Zhang, Xiaoli Lan, Yongkang Gai
Abstract
Nowadays, pancreatic cancer is still a formidable disease to diagnose. The CXC chemokine receptor 4 (CXCR4) and integrin αvβ3 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 68Ga-yG5-RGD targeting both CXCR4 and integrin αvβ3, and evaluated its feasibility and utility in PET imaging of pancreatic cancer. The 68Ga-yG5-RGD could accumulate in CXCR4/integrin αvβ3 positive BxPC3 tumors in a high concentration and was much higher than that of 68Ga-yG5 (p < 0.001) and 68Ga-RGD (p < 0.001). No increased uptake of 68Ga-yG5-RGD was found in MX-1 tumors (CXCR4/integrin αvβ3, negative). In addition, the uptake of 68Ga-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 68Ga-yG5-RGD is a promising tracer for the noninvasive detection of tumors that express either CXCR4 or integrin αvβ3 or both, and therefore may have good prospects for clinical translation.