In Vivo Imaging of Ischemia/Reperfusion-mediated Aminopeptidase N Expression in Surgical Rat Model Using 68Ga-NOTA-c(NGR)

In Vivo. 2022 Mar-Apr;36(2):657-666. doi: 10.21873/invivo.12750.

Abstract

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.

Keywords: 68Ga-NOTA-c(NGR); Aminopeptidase N; Angiogenesis; NGR peptide; ischemia/reperfusion; positron emission tomography.

MeSH terms

  • Animals
  • CD13 Antigens* / metabolism
  • Cell Line, Tumor
  • Gallium Radioisotopes*
  • Heterocyclic Compounds, 1-Ring
  • Ischemia
  • Positron-Emission Tomography / methods
  • Rats
  • Reperfusion

Substances

  • Gallium Radioisotopes
  • Heterocyclic Compounds, 1-Ring
  • 1,4,7-triazacyclononane-N,N',N''-triacetic acid
  • CD13 Antigens