Dataset Information

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

ABSTRACT: 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 (p < 0.001) and ⁶⁸Ga-RGD (p < 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 (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 α_vβ₃ or both, and therefore may have good prospects for clinical translation.

SUBMITTER: Jiang Y

PROVIDER: S-EPMC9503769 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Development and Evaluation of a Peptide Heterodimeric Tracer Targeting CXCR4 and Integrin α<sub>v</sub>β<sub>3</sub> for Pancreatic Cancer Imaging.

Jiang Yaqun Y Long Yu Y Ji Hao H Qiao Pengxin P Liu Qingyao Q Xia Xiaotian X Qin Chunxia C Zhang Yongxue Y Lan Xiaoli X Gai Yongkang Y

Pharmaceutics 20220826 9

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 α ...[more]

PMID: 36145541

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Project description:Integrin αvβ3 and aminopeptidase N (APN, also known as CD13) are two important targets involved in the regulation of angiogenesis, tumor proliferation, invasion, and metastasis. In this study, we developed a heterodimeric tracer consisting of arginine-glycine-aspartic (RGD) and asparagine-glycine-arginine (NGR) peptides targeting αvβ3 and CD13, respectively, for PET imaging of breast cancer. The NGR peptide was first modified with N3-NOtB2 and then conjugated to BCN-PEG4-c(RGDyK) via copper-free click chemistry. The resulting precursor was purified and radiolabeled with gallium-68. Small-animal PET/CT imaging and post-imaging biodistribution studies were performed in mice bearing human breast cancer MCF-7, MDA-MB-231, MDA-MB-468, and MX-1 xenografts and pulmonary metastases models. The expression levels of αvβ3 and CD13 in tumors were checked via immunochemical staining. The heterodimeric tracer was successfully synthesized and radiolabeled with gallium-68 at a molar activity of 45-100 MBq/nmol at the end of synthesis. It demonstrated high in vitro and in vivo stability. In static PET/CT imaging studies, the MCF-7 tumor could be clearly visualized and exhibited higher uptake at 30 min post injection of 68Ga-NGR-RGD than that of either 68Ga-RGD or 68Ga-NGR alone. High specificity was shown in blocking studies using Arg-Gly-Asp (RGD) and Asp-Gly-Arg (NGR) peptides. The MCF-7 tumor exhibited the highest uptake of 68Ga-NGR-RGD followed by MDA-MB-231, MDA-MB-468, and MX-1 tumors. This was consistent with their expression levels of CD13 and αvβ3 as confirmed by western blot and immunohistochemical staining. Metastatic lesions in the lungs were clearly detectable on 68Ga-NGR-RGD PET/CT imaging in mouse models of pulmonary metastases. 68Ga-NGR-RGD, a CD13 and αvβ3 dual-receptor targeting tracer, showed higher binding avidities, targeting efficiency, and longer tumor retention time compared with monomeric 68Ga-NGR and 68Ga-RGD. Its promising in vivo performance makes it an ideal candidate for future clinical translation.

Dataset Information

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

Publications

Development and Evaluation of a Peptide Heterodimeric Tracer Targeting CXCR4 and Integrin α<sub>v</sub>β<sub>3</sub> for Pancreatic Cancer Imaging.

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Dataset Information

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

Publications

Development and Evaluation of a Peptide Heterodimeric Tracer Targeting CXCR4 and Integrin α<sub>v</sub>β<sub>3</sub> for Pancreatic Cancer Imaging.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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