In vivo Molecular Imaging of Glutamate Carboxypeptidase II Expression in Re-endothelialisation after Percutaneous Balloon Denudation in a Rat Model

Sci Rep. 2018 May 9;8(1):7411. doi: 10.1038/s41598-018-25863-1.

Abstract

The short- and long-term success of intravascular stents depends on a proper re-endothelialisation after the intervention-induced endothelial denudation. The aim of this study was to evaluate the potential of in vivo molecular imaging of glutamate carboxypeptidase II (GCPII; identical with prostate-specific membrane antigen PSMA) expression as a marker of re-endothelialisation. Fifteen Sprague Dawley rats underwent unilateral balloon angioplasty of the common carotid artery (CCA). Positron emission tomography (PET) using the GCPII-targeting tracer [18F]DCFPyL was performed after 5-21 days (scan 60-120 min post injection). In two animals, the GCPII inhibitor PMPA (23 mg/kg BW) was added to the tracer solution. After PET, both CCAs were removed, dissected, and immunostained with the GCPII specific antibody YPSMA-1. Difference of GCPII expression between both CCAs was established by PCR analysis. [18F]DCFPyL uptake was significantly higher in the ipsilateral compared to the contralateral CCA with an ipsi-/contralateral ratio of 1.67 ± 0.39. PMPA blocked tracer binding. The selective expression of GCPII in endothelial cells of the treated CCA was confirmed by immunohistological staining. PCR analysis verified the site-specific GCPII expression. By using a molecular imaging marker of GCPII expression, we provide the first non-invasive in vivo delineation of re-endothelialisation after angioplasty.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angioplasty, Balloon, Coronary*
  • Animals
  • Carotid Artery, Common / diagnostic imaging
  • Carotid Artery, Common / surgery
  • Disease Models, Animal
  • Endothelial Cells / cytology*
  • Gene Expression Regulation, Enzymologic*
  • Glutamate Carboxypeptidase II / genetics*
  • Glutamate Carboxypeptidase II / metabolism*
  • Male
  • Positron-Emission Tomography*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Glutamate Carboxypeptidase II