In vivo imaging of Aminopeptidase N (CD13) receptors in experimental renal tumors using the novel radiotracer 68Ga-NOTA-c(NGR)

Máté, Gábor and Kertész, István and Enyedi, Kata N. and Mező, Gábor and Angyal, János and Vasas, Nikolett and Kiss, Adrienn and Szabó, Éva and Emri, Miklós and Bíró, Tamás and Galuska, László and Trencsényi, György (2015) In vivo imaging of Aminopeptidase N (CD13) receptors in experimental renal tumors using the novel radiotracer 68Ga-NOTA-c(NGR). EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 69. pp. 61-71. ISSN 0928-0987

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Abstract

Purpose: Aminopeptidase N (APN/CD13) plays an important role in tumor neoangiogenic process and the development of metastases. Furthermore, it may serve as a potential target for cancer diagnosis and therapy. Previous studies have already shown that asparagine–glycine–arginine (NGR) peptides specifically bind to APN/CD13. The aim of the study was to synthesize and investigate the APN/CD13 specificity of a novel 68Ga-labeled NOTA-c(NGR) molecule in vivo using miniPET. Methods: c[KNGRE]-NH2 peptide was conjugated with p-SCN-Bn-NOTA and was labeled with Ga-68 (68Ga-NOTA-c(NGR)). Orthotopic and heterotopic transplanted mesoblastic nephroma (NeDe) bearing Fischer-344 rats were prepared, on which biodistribution studies and miniPET scans were performed for both 68Ga-NOTA-c(NGR) and amb3 integrin selective 68Ga-NODAGA-[c(RGD)]2 tracers. APN/CD13 receptor expression of NeDe tumors and metastases was analyzed by western blot. Results: 68Ga-NOTA-c(NGR) was produced with high specific activity (5.13–5.92 GBq/lmol) and with excellent radiochemical purity (95%<), at all cases. Biodistribution studies in normal rats showed that uptake of the 68Ga-NOTA-c(NGR) was significantly (p 6 0.05) lower in abdominal organs in comparison with 68Ga-NODAGA-[c(RGD)]2. Both radiotracers were mainly excreted from the kidney. In NeDe tumor bearing rats higher 68Ga-NOTA-c(NGR) accumulation was found in the tumors than that of the 68Ga-NODAGA-[ c(RGD)]2. Using orthotopic transplantation, metastases were developed which showed specific 68Ga-NOTA-c(NGR) uptake. Western blot analysis confirmed the presence of APN/CD13 expression in NeDe tumors and metastases.

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