In Vivo Imaging of Acute Hindlimb Ischaemia in Rat Model: A Pre-Clinical PET Study
Gergely Farkasinszky,
Judit Szabó Péliné,
Péter Károlyi,
Szilvia Rácz,
Noémi Dénes,
Tamás Papp,
József Király,
Zsuzsanna Szabo,
István Kertész,
Gábor Mező,
Gabor Halmos,
Zita Képes,
György Trencsényi
Affiliations
Gergely Farkasinszky
Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
Judit Szabó Péliné
Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
Péter Károlyi
Doctoral School of Neuroscience, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary
Szilvia Rácz
Division of Radiology, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
Noémi Dénes
Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
Tamás Papp
Doctoral School of Neuroscience, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary
József Király
Department of Biopharmacy, Faculty of Pharmacy, University of Debrecen, H-4032 Debrecen, Hungary
Zsuzsanna Szabo
Department of Biopharmacy, Faculty of Pharmacy, University of Debrecen, H-4032 Debrecen, Hungary
István Kertész
Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
Gábor Mező
Institute of Chemistry, Faculty of Science, Eötvös Loránd University, H-1053 Budapest, Hungary
Gabor Halmos
Department of Biopharmacy, Faculty of Pharmacy, University of Debrecen, H-4032 Debrecen, Hungary
Zita Képes
Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
György Trencsényi
Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
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.
