PT  - JOURNAL ARTICLE
AU  - JUDIT P. SZABO
AU  - NOEMI DENES
AU  - VIKTORIA ARATO
AU  - SZILVIA RACZ
AU  - ADRIENN KIS
AU  - GABOR OPPOSITS
AU  - ZITA KEPES
AU  - ISTVAN HAJDU
AU  - ISTVAN JOSZAI
AU  - MIKLOS EMRI
AU  - ISTVAN KERTESZ
AU  - GABOR MEZO
AU  - GYORGY TRENCSENYI
TI  - <em>In Vivo</em> Imaging of Neo-angiogenesis of Transplanted Metastases in Subrenal Capsule Assay Induced Rat Model
AID  - 10.21873/invivo.12878
DP  - 2022 Jul 01
TA  - In Vivo
PG  - 1667--1675
VI  - 36
IP  - 4
4099  - http://iv.iiarjournals.org/content/36/4/1667.short
4100  - http://iv.iiarjournals.org/content/36/4/1667.full
SO  - In Vivo2022 Jul 01; 36
AB  - 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.