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

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