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

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 68 Ga-labeled NOTA-c(NGR) molecule in vivo using miniPET. Methods c[KNGRE]-NH 2 peptide was conjugated with p -SCN-Bn-NOTA and was labeled with Ga-68 ( 68 Ga-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 68 Ga-NOTA-c(NGR) and α ν β 3 integrin selective 68 Ga-NODAGA-[c(RGD)] 2 tracers. APN/CD13 receptor expression of NeDe tumors and metastases was analyzed by western blot. Results 68 Ga-NOTA-c(NGR) was produced with high specific activity (5.13–5.92 GBq/μmol) and with excellent radiochemical purity (95% 68 Ga-NOTA-c(NGR) was significantly ( p  ⩽ 0.05) lower in abdominal organs in comparison with 68 Ga-NODAGA-[c(RGD)] 2 . Both radiotracers were mainly excreted from the kidney. In NeDe tumor bearing rats higher 68 Ga-NOTA-c(NGR) accumulation was found in the tumors than that of the 68 Ga-NODAGA-[c(RGD)] 2 . Using orthotopic transplantation, metastases were developed which showed specific 68 Ga-NOTA-c(NGR) uptake. Western blot analysis confirmed the presence of APN/CD13 expression in NeDe tumors and metastases. Conclusion Our novel radiotracer 68 Ga-NOTA-c(NGR) showed specific binding to the APN/CD13 expressed ortho- and heterotopic transplanted NeDe tumors. Therefore, 68 Ga-NOTA-c(NGR) is a suitable tracer for the detection of APN/CD13 positive tumors and metastases in vivo .