In Vivo Molecular Imaging of the Efficacy of Aminopeptidase N (APN/CD13) Receptor Inhibitor Treatment on Experimental Tumors Using 68 Ga-NODAGA-c(NGR) Peptide.

Autor:	Kis A; Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary.; Doctoral School of Clinical Medicine, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary., Dénes N; Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary.; Gyula Petrányi Doctoral School of Allergy and Clinical Immunology, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary., Szabó JP; Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary.; Doctoral School of Clinical Medicine, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary., Arató V; Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary., Beke L; Department of Pathology, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary., Matolay O; Department of Pathology, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary., Enyedi KN; Eötvös Loránd University, Faculty of Science, Institute of Chemistry, Budapest, Hungary., Méhes G; Department of Pathology, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary., Mező G; Eötvös Loránd University, Faculty of Science, Institute of Chemistry, Budapest, Hungary.; MTA-ELTE, Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös L. University, Budapest, Hungary., Bai P; Department of Medical Chemistry, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary.; MTA-DE Lendület Laboratory of Cellular Metabolism, Debrecen, Hungary.; Research Center for Molecular Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary., Kertész I; Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary., Trencsényi G; Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary.; Doctoral School of Clinical Medicine, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary.; Gyula Petrányi Doctoral School of Allergy and Clinical Immunology, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary.
Jazyk:	angličtina
Zdroj:	BioMed research international [Biomed Res Int] 2021 Mar 10; Vol. 2021, pp. 6642973. Date of Electronic Publication: 2021 Mar 10 (Print Publication: 2021).
DOI:	10.1155/2021/6642973
Abstrakt:	Introduction: The aminopeptidase N (APN/CD13) receptor plays an important role in the neoangiogenic process and metastatic tumor cell invasion. Clinical and preclinical studies reported that bestatin and actinonin are cytotoxic to APN/CD13-positive tumors and metastases due to their APN/CD13-specific inhibitor properties. Our previous studies have already shown that ⁶⁸ Ga-labeled NGR peptides bind specifically to APN/CD13 expressing tumor cells. The APN/CD13 specificity of ⁶⁸ Ga-NGR radiopharmaceuticals enables the following of the efficacy of antiangiogenic therapy with APN/CD13-specific inhibitors using positron emission tomography (PET). The aim of this in vivo study was to assess the antitumor effect of bestatin and actinonin treatment in subcutaneous transplanted HT1080 and B16-F10 tumor-bearing animal models using ⁶⁸ Ga-NODAGA-c(NGR). Materials and Methods: Three days after the inoculation of HT1080 and B16-F10 cells, mice were treated with intraperitoneal injection of bestatin (15 mg/kg) or actinonin (5 mg/kg) for 7 days. On the 5 ^th and 10 ^th day, in vivo PET scans and ex vivo biodistribution studies were performed 90 min after intravenous injection of 5.5 ± 0.2 MBq ⁶⁸ Ga-NODAGA-c(NGR). Results: Control-untreated HT1080 and B16-F10 tumors were clearly visualized by the APN/CD13-specific ⁶⁸ Ga-NODAGA-c(NGR) radiopharmaceutical. The western blot analysis also confirmed the strong APN/CD13 positivity in the investigated tumors. We found significantly ( p ≤ 0.05) lower radiopharmaceutical uptake after bestatin treatment and higher radiotracer accumulation in the actinonin-treated HT1080 tumors. In contrast, significantly lower ( p ≤ 0.01) ⁶⁸ Ga-NODAGA-c(NGR) accumulation was observed in both bestatin- and actinonin-treated B16-F10 melanoma tumors compared to the untreated-control tumors. Bestatin inhibited tumor growth and ⁶⁸ Ga-NODAGA-c(NGR) uptake in both tumor models. Conclusion: The bestatin treatment is suitable for suppressing the neoangiogenic process and APN/CD13 expression of experimental HT1080 and B16-F10 tumors; furthermore, ⁶⁸ Ga-NODAGA-c(NGR) is an applicable radiotracer for the in vivo monitoring of the efficacy of the APN/CD13 inhibition-based anticancer therapies. Competing Interests: We declare that we have no conflict of interest. (Copyright © 2021 Adrienn Kis et al.)
Databáze:	MEDLINE
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