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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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2.

001-es BibID:BIBFORM087404
035-os BibID:(cikkazonosító)4952372 (WOS)000562881800004 (Scopus)85089974115
Első szerző:Kis Adrienn (molekuláris biológus)
Cím:In vivo Imaging of Hypoxia and Neoangiogenesis in Experimental Syngeneic Hepatocellular Carcinoma Tumor Model Using Positron Emission Tomography / Adrienn Kis, Judit P. Szabó, Noémi Dénes, Adrienn Vágner, Gábor Nagy, Ildikó Garai, Anikó Fekete, Dezső Szikra, István Hajdu, Orsolya Matolay, Gábor Méhes, Gábor Mező, István Kertész, György Trencsényi
Dátum:2020
ISSN:2314-6133 2314-6141
Megjegyzések:Introduction. Hypoxia-induced alpha(nu)beta(3)integrin and aminopeptidase N (APN/CD13) receptor expression play an important role in tumor neoangiogenesis. APN/CD13-specific(68)Ga-NOTA-c(NGR),alpha(nu)beta(3)integrin-specific(68)Ga-NODAGA-[c(RGD)](2), and hypoxia-specific(68)Ga-DOTA-nitroimidazole enable thein vivodetection of the neoangiogenic process and the hypoxic regions in the tumor mass using positron emission tomography (PET) imaging. The aim of this study was to evaluate whether(68)Ga-NOTA-c(NGR) and(68)Ga-DOTA-nitroimidazole allow thein vivononinvasive detection of the temporal changes of APN/CD13 expression and hypoxia in experimental He/De tumors using positron emission tomography.Materials and Methods.5x106hepatocellular carcinoma (He/De) cells were used for the induction of a subcutaneous tumor model in Fischer-344 rats. He/De tumor-bearing animals were anaesthetized, and 90 min after intravenous injection of10.2 +/- 1.1 MBq(68)Ga-NOTA-c(NGR) or(68)Ga-NODAGA-[c(RGD)](2)(as angiogenesis tracers) or(68)Ga-DOTA-nitroimidazole (for hypoxia imaging), whole-body PET/MRI scans were performed.Results. Hypoxic regions and angiogenic markers (alpha(v)beta(3)integrin and APN/CD13) were determined using(68)Ga-NOTA-c(NGR),Ga-68-DOTA-nitroimidazole, and(68)Ga-NODAGA-[c(RGD)](2)in subcutaneously growing He/De tumors in rats.Ga-68-NOTA-c(NGR) showed the strong APN/CD13 positivity of He/De tumorsin vivo, by which observation was confirmed by western blot analysis. By the qualitative analysis of PET images, heterogenous accumulation was found inside He/De tumors using all radiotracers. Significantly (p <= 0.01) higher SUVmean and SUVmax values were found in the radiotracer avid regions of the tumors than those of the nonavid areas using hypoxia and angiogenesis-specific radiopharmaceuticals. Furthermore, a strong correlation was found between the presence of angiogenic markers, the appearance of hypoxic regions, and the tumor volume using noninvasivein vivoPET imaging.Conclusion.Ga-68-DOTA-nitroimidazole and(68)Ga-NOTA-c(NGR) are suitable diagnostic radiotracers for the detection of the temporal changes of hypoxic areas and neoangiogenic molecule (CD13) expression, which vary during tumor growth in a hepatocellular carcinoma model.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
angiogenezis
Aminopeptidáz N
NGR
hypoxia
PET
Megjelenés:Biomed Research International. - 2020 (2020), p. 1-10. -
További szerzők:Péli-Szabó Judit (1977-) (vegyész) Dénes Noémi (1992-) (vegyész) Vágner Adrienn (1990-) (vegyész, kémikus) Nagy Gábor (1990-) (radiokémikus, vegyész) Garai Ildikó (1966-) (radiológus) Fekete Anikó (1973-) (vegyész) Szikra Dezső Péter (1983-) (vegyész) Hajdu István (1981-) (vegyész) Matolay Orsolya (1989-) Méhes Gábor (1966-) (patológus) Mező Gábor (1959-) (vegyész) Kertész István (1966-) (vegyész) Trencsényi György (1978-) (biológus, biokémikus, molekuláris biológus)
Pályázati támogatás:Tématerületi Kiválósági Program ED_18-1-2019-0028
Egyéb
EFOP-3.6.3-VEKOP-16-2017-00009
EFOP
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:
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