Development and Evaluation of a Peptide Heterodimeric Tracer Targeting CXCR4 and Integrin αvβ3 for Pancreatic Cancer Imaging

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 hetero...

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Published in:Pharmaceutics 2022-08, Vol.14 (9), p.1791
Main Authors: Jiang, Yaqun, Long, Yu, Ji, Hao, Qiao, Pengxin, Liu, Qingyao, Xia, Xiaotian, Qin, Chunxia, Zhang, Yongxue, Lan, Xiaoli, Gai, Yongkang
Format: Article
Language:English
Subjects:
Angiogenesis
Biomarkers
Breast cancer
C-X-C chemokine receptor type 4
Cancer therapies
Efficiency
integrin αvβ3
Mass spectrometry
Metastasis
Pancreatic cancer
peptide heterodimer
Peptides
Prostate
Proteins
Scientific imaging
Tumors
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Summary: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.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics14091791