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

doi:10.3390/pharmaceutics16040542

In Vivo Imaging of Acute Hindlimb Ischaemia in Rat Model: A Pre-Clinical PET Study

Pharmaceutics. 2024 Apr 15;16(4):542. doi: 10.3390/pharmaceutics16040542.

Authors

Gergely Farkasinszky^{1

2}, Judit Szabó Péliné¹, Péter Károlyi^{3

4}, Szilvia Rácz⁵, Noémi Dénes¹, Tamás Papp^{3

4}, József Király⁶, Zsuzsanna Szabo⁶, István Kertész¹, Gábor Mező^{7

8}, Gabor Halmos⁶, Zita Képes^{1

2}, György Trencsényi^{1

2}

Affiliations

¹ Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary.
² Gyula Petrányi Doctoral School of Allergy and Clinical Immunology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary.
³ Doctoral School of Neuroscience, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary.
⁴ Division of Radiology and Imaging Science, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary.
⁵ Division of Radiology, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary.
⁶ Department of Biopharmacy, Faculty of Pharmacy, University of Debrecen, H-4032 Debrecen, Hungary.
⁷ Institute of Chemistry, Faculty of Science, Eötvös Loránd University, H-1053 Budapest, Hungary.
⁸ MTA-ELTE, Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös L. University, H-1053 Budapest, Hungary.

Abstract

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.

Keywords: 2-[18F]FDG; Peripheral Arterial Disease (PAD); [68Ga]Ga-NOTA-c(NGR); aminopeptidase N (APN/CD13); angiogenesis; ischaemia; positron emission tomography (PET); preclinical.

Abstract

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