In vivo imaging of Aminopeptidase N (CD13) receptors in experimental renal tumors using the novel radiotracer 68Ga-NOTA-c(NGR)
| Autor: | Adrienn Kis, Gábor Máté, Kata Nóra Enyedi, István Kertész, Gábor Mező, Nikolett Vasas, Tamás Bíró, László Galuska, Miklós Emri, Éva Szabó, János Angyal, György Trencsényi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Biodistribution Receptor expression Integrin Pharmaceutical Science CD13 Antigens Klinikai orvostudományok Peptides Cyclic chemistry.chemical_compound Western blot Coordination Complexes In vivo medicine Animals DOTA Tissue Distribution Radioactive Tracers Receptor biology medicine.diagnostic_test Chemistry Orvostudományok Kidney Neoplasms Rats Inbred F344 Biochemistry Positron-Emission Tomography Cancer research biology.protein Preclinical imaging |
| Popis: | 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.c[KNGRE]-NH2 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 ανβ3 integrin selective (68)Ga-NODAGA-[c(RGD)]2 tracers. APN/CD13 receptor expression of NeDe tumors and metastases was analyzed by western blot.(68)Ga-NOTA-c(NGR) was produced with high specific activity (5.13-5.92GBq/μmol) and with excellent radiochemical purity (95%), at all cases. Biodistribution studies in normal rats showed that uptake of the (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.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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|