Background/Aim: Changes in the expression of neoangiogenic 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 α v β 3 integrin receptor expression in serially transplanted mesoblastic nephroma tumor (Ne/De) metastases using 68 Gallium ( 68 Ga)-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 68 Ga-NOTA-c(NGR), 68 Ga-NODAGA-RGD, and [ 18 F]FDG radiotracers. Results: Among the examined neo-angiogenic molecules, the expression of α v β 3 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 68 Ga-NOTA-cNGR accumulation was observed in both primary malignancies and metastases. However, a steadily increased accumulation of [ 18 F]FDG, 68 Ga-NODAGA-RGD, and 68 Ga-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 68 Ga-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 α v β 3 integrin and APN/CD13 during serial transplantations of metastases may indicate enhanced malignancy.

Background/Aim: Previous studies have already shown that 68 Gallium( 68 Ga)-labeled NGR-based radiopharmaceuticals specifically bind to the neoangiogenic molecule Aminopeptidase N (APN/CD13). The aim of this study was to evaluate the applicability of 68 Ga-NOTAc(NGR) in the in vivo detection of the temporal changes of APN/CD13 expression in the diabetic retinopathy rat model using positron emission tomography (PET). Materials and Methods: Ischemia/reperfusion injury was initiated by surgical ligation of the left bulbus oculi of rats. In vivo PET imaging studies were performed after the surgery using 68 Ga-NOTA-c(NGR). Results: Significantly higher 68 Ga-NOTA-c(NGR) uptake was observed in the surgically-ligated left bulbus, compared to the bulbus of the non-surgical group at each investigated time point. The western blot and histological analysis confirmed the increased expression of the neo-angiogenic marker APN/CD13. Conclusion: 68 Ga-NOTA-c(NGR) is a suitable radiotracer for the detection of the temporal changes of the ischemia/reperfusion-mediated expression of APN/CD13 in the surgically induced diabetic retinopathy rat model.Diabetes mellitus (DM) belongs to the cluster of metabolic disorders, characterized by hyperglycemia over a prolonged interlude. Symptoms of hyperglycemia include polyuria, polydipsia, and polyphagia (1, 2). DM may cause many acute or severe complications (3), such as cardiovascular disease, stroke, chronic kidney failure, neuropathy and diabetic retinopathy (DR) (2, 4). DR is one of the most common microvascular complications of diabetes. In 2015, there were more than 414 million people affected by some form of diabetes. According to certain predictions, the number of diabetic patients will have extended to 641 million in 2040 (5). Diabetes can generally be divided into three types: i) insulin-dependent, ii) insulin-independent and iii) gestational, although, all patients commonly experience hyperglycemia. According to the current scientific evidence, approximately 33% of diabetic patients have signs of DR and approximately 10% of them even develop visionthreatening retinopathy (6). Clinically, DR-induced 657 This article is freely accessible online.