RESUMO
BACKGROUND: To better understand ischaemia-related molecular alterations, temporal changes in angiogenic Aminopeptidase N (APN/CD13) expression and glucose metabolism were assessed with PET using a rat model of peripheral arterial disease (PAD). METHODS: The mechanical occlusion of the base of the left hindlimb triggered using a tourniquet was applied to establish the ischaemia/reperfusion injury model in Fischer-344 rats. 2-[18F]FDG and [68Ga]Ga-NOTA-c(NGR) PET imaging performed 1, 3, 5, 7, and 10 days post-ischaemia induction was followed by Western blotting and immunohistochemical staining for APN/CD13 in ischaemic and control muscle tissue extracts. RESULTS: Due to a cellular adaptation to hypoxia, a gradual increase in [68Ga]Ga-NOTA-c(NGR) and 2-[18F]FDG uptake was observed from post-intervention day 1 to 7 in the ischaemic hindlimbs, which was followed by a drop on day 10. Conforming pronounced angiogenic recovery, the NGR accretion of the ischaemic extremities differed significantly from the controls 5, 7, and 10 days after ischaemia induction (p ≤ 0.05), which correlated with the Western blot and immunohistochemical results. No remarkable radioactivity was depicted between the normally perfused hindlimbs of either the ischaemic or the control groups. CONCLUSIONS: The PET-based longitudinal assessment of angiogenesis-associated APN/CD13 expression and glucose metabolism during ischaemia may continue to broaden our knowledge on the pathophysiology of PAD.
RESUMO
BACKGROUND/AIM: Previous studies have already shown that 68Gallium(68Ga)-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 68Ga-NOTA-c(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 68Ga-NOTA-c(NGR). RESULTS: Significantly higher 68Ga-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: 68Ga-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.
