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001-es BibID:BIBFORM092257
035-os BibID:(cikkazonosító)6642973 (WOS)000631875000006 (Scopus)85103189686
Első szerző:Kis Adrienn (molekuláris biológus)
Cím:In Vivo Molecular Imaging of the Efficacy of Aminopeptidase N (APN/CD13) Receptor Inhibitor Treatment on Experimental Tumors Using 68Ga-NODAGA-c(NGR) Peptide / Adrienn Kis, Noémi Dénes, Judit P. Szabó, Viktória Arató, Lívia Beke, Orsolya Matolay, Kata Nóra Enyedi, Gábor Méhes, Gábor Mező, Péter Bai, István Kertész, György Trencsényi
Dátum:2021
ISSN:2314-6133 2314-6141
Megjegyzések: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 Ga-68-labeled NGR peptides bind specifically to APN/CD13 expressing tumor cells. The APN/CD13 specificity of Ga-68-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 Ga-68-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 5th and 10th 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 Ga-68-NODAGA-c(NGR) radiopharmaceutical. The western blot analysis also confirmed the strong APN/CDI3 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) Ga-68-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 Ga-68-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, Ga-68-NODAGA-c(NGR) is an applicable radiotracer for the in vivo monitoring of the efficacy of the APN/CD13 inhibition-based anticancer therapies.
Tárgyszavak:Orvostudományok Egészségtudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:BioMed Research International. - 2021 (2021), p. 1-11. -
További szerzők:Dénes Noémi (1992-) (vegyész) Péli-Szabó Judit (1977-) (vegyész) Arató Viktória Zsófia (1989-) (gyógyszerész) Beke Lívia Matolay Orsolya (1989-) Enyedi Kata Nóra (1987-) (vegyész) Méhes Gábor (1966-) (patológus) Mező Gábor (1959-) (vegyész) Bai Péter (1976-) (biokémikus) Kertész István (1966-) (vegyész) Trencsényi György (1978-) (biológus, biokémikus, molekuláris biológus)
Pályázati támogatás:NKFIH K119552
NKFIH
NVKP_16-1-2016-0036
Egyéb
EFOP-3.6.3-VEKOP-16-2017-00009
EFOP
Internet cím:DOI
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