Development and Evaluation of a Peptide Heterodimeric Tracer Targeting CXCR4 and Integrin α_vβ₃ for Pancreatic Cancer Imaging

• Main Authors: Yaqun Jiang (Author), Yu Long (Author), Hao Ji (Author), Pengxin Qiao (Author), Qingyao Liu (Author), Xiaotian Xia (Author), Chunxia Qin (Author), Yongxue Zhang (Author), Xiaoli Lan (Author), Yongkang Gai (Author)
• Format: Book
• Published: MDPI AG, 2022-08-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Nowadays, pancreatic cancer is still a formidable disease to diagnose. The CXC chemokine receptor 4 (CXCR4) and integrin α_vβ₃ 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 α_vβ₃, and evaluated its feasibility and utility in PET imaging of pancreatic cancer. The ⁶⁸Ga-yG5-RGD could accumulate in CXCR4/integrin α_vβ₃ positive BxPC3 tumors in a high concentration and was much higher than that of ⁶⁸Ga-yG5 (<i>p</i> < 0.001) and ⁶⁸Ga-RGD (<i>p</i> < 0.001). No increased uptake of ⁶⁸Ga-yG5-RGD was found in MX-1 tumors (CXCR4/integrin α_vβ₃, 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 (<i>p</i> < 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 α_vβ₃ or both, and therefore may have good prospects for clinical translation.

Item Description

10.3390/pharmaceutics14091791
1999-4923