Judit P Szabo1,2, Noemi Denes1, Viktoria Arato1, Szilvia Racz3, Adrienn Kis1, Gabor Opposits1, Zita Kepes1, Istvan Hajdu1, Istvan Joszai1, Miklos Emri1, Istvan Kertesz1, Gabor Mezo4,5, Gyorgy Trencsenyi6,2. 1. Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. 2. Doctoral School of Clinical Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. 3. Division of Radiology, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. 4. Eötvös Loránd University, Faculty of Science, Institute of Chemistry, Budapest, Hungary. 5. MTA-ELTE, Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös L. University, Budapest, Hungary. 6. Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; trencsenyi.gyorgy@med.unideb.hu.
Abstract
BACKGROUND/AIM: Changes in the expression of neo-angiogenic molecules in the primary tumor and its metastases may significantly affect the efficacy of therapies. The aim of this study was to evaluate the alterations in aminopeptidase N (APN/CD13) and αvβ3 integrin receptor expression in serially transplanted mesoblastic nephroma tumor (Ne/De) metastases using 68Gallium (68Ga)-labeled NOTA-cNGR and NODAGA-RGD radiotracers and preclinical positron emission tomography (PET) imaging. MATERIALS AND METHODS: Primary and metastatic mesoblastic nephroma (Ne/De) tumors were induced by subrenal capsule assay (SRCA) in Fischer-344 rats. In vivo PET imaging experiments were performed 8±1 days after the SRCA surgery using intravenously injected 68Ga-NOTA-c(NGR), 68Ga-NODAGA-RGD, and [18F]FDG radiotracers. RESULTS: Among the examined neo-angiogenic molecules, the expression of αvß3 integrin in the tumors was significantly lower than that of APN/CD13. This observation was confirmed by the PET data analysis, where a 2-6-fold higher APN/CD13-specific 68Ga-NOTA-cNGR accumulation was observed in both primary malignancies and metastases. However, a steadily increased accumulation of [18F]FDG, 68Ga-NODAGA-RGD, and 68Ga-NOTA-cNGR was observed in the tumors growing under the renal capsule and in the metastatic parathymic lymph nodes during serial transplantations. The observed increase in 68Ga- NOTA-cNGR accumulation during serial transplantations correlated well with the western blot analysis, where APN/CD13 protein levels were also elevated in the metastatic parathymic lymph nodes. CONCLUSION: The observed increase in glucose metabolism and the up-regulated expression of αvß3 integrin and APN/CD13 during serial transplantations of metastases may indicate enhanced malignancy.
BACKGROUND/AIM: Changes in the expression of neo-angiogenic molecules in the primary tumor and its metastases may significantly affect the efficacy of therapies. The aim of this study was to evaluate the alterations in aminopeptidase N (APN/CD13) and αvβ3 integrin receptor expression in serially transplanted mesoblastic nephroma tumor (Ne/De) metastases using 68Gallium (68Ga)-labeled NOTA-cNGR and NODAGA-RGD radiotracers and preclinical positron emission tomography (PET) imaging. MATERIALS AND METHODS: Primary and metastatic mesoblastic nephroma (Ne/De) tumors were induced by subrenal capsule assay (SRCA) in Fischer-344 rats. In vivo PET imaging experiments were performed 8±1 days after the SRCA surgery using intravenously injected 68Ga-NOTA-c(NGR), 68Ga-NODAGA-RGD, and [18F]FDG radiotracers. RESULTS: Among the examined neo-angiogenic molecules, the expression of αvß3 integrin in the tumors was significantly lower than that of APN/CD13. This observation was confirmed by the PET data analysis, where a 2-6-fold higher APN/CD13-specific 68Ga-NOTA-cNGR accumulation was observed in both primary malignancies and metastases. However, a steadily increased accumulation of [18F]FDG, 68Ga-NODAGA-RGD, and 68Ga-NOTA-cNGR was observed in the tumors growing under the renal capsule and in the metastatic parathymic lymph nodes during serial transplantations. The observed increase in 68Ga- NOTA-cNGR accumulation during serial transplantations correlated well with the western blot analysis, where APN/CD13 protein levels were also elevated in the metastatic parathymic lymph nodes. CONCLUSION: The observed increase in glucose metabolism and the up-regulated expression of αvß3 integrin and APN/CD13 during serial transplantations of metastases may indicate enhanced malignancy.
Authors: Adrienn Kis; Noémi Dénes; Judit P Szabó; Viktória Arató; István Jószai; Kata Nóra Enyedi; Szilvia Lakatos; Ildikó Garai; Gábor Mező; István Kertész; György Trencsényi Journal: Int J Pharm Date: 2020-09-16 Impact factor: 5.875
Authors: Gábor Máté; István Kertész; Kata Nóra Enyedi; Gábor Mező; János Angyal; Nikolett Vasas; Adrienn Kis; Éva Szabó; Miklós Emri; Tamás Bíró; László Galuska; György Trencsényi Journal: Eur J Pharm Sci Date: 2015-01-13 Impact factor: 4.384