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.

Details

Title
In vivo Molecular Imaging of Glutamate Carboxypeptidase II Expression in Re-endothelialisation after Percutaneous Balloon Denudation in a Rat Model
Author
Endepols, Heike 1   VIAFID ORCID Logo  ; Mottaghy, Felix M 2 ; Simsekyilmaz, Sakine 3 ; Bucerius, Jan 4 ; Vogt, Felix 5 ; Winz, Oliver 6 ; Richarz, Raphael 7 ; Krapf, Philipp 8 ; Neumaier, Bernd 9   VIAFID ORCID Logo  ; Zlatopolskiy, Boris D 10 ; Morgenroth, Agnieszka 6 

1  Institute of Radiochemistry and Experimental Molecular Imaging (IREMB), University Hospital of Cologne, Cologne, Germany; Department of Nuclear Medicine, University Hospital of Cologne, Cologne, Germany 
2  Department of Nuclear Medicine, University Hospital, RWTH Aachen, Aachen, Germany; Department of Nuclear Medicine, Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands 
3  Institute for Molecular Cardiovascular Research, University Hospital, RWTH Aachen, Aachen, Germany 
4  Department of Nuclear Medicine, University Hospital, RWTH Aachen, Aachen, Germany; Department of Nuclear Medicine, Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands 
5  Department of Cardiology, Pneumology, Angiology, and Internal Intensive Care Medicine, University Hospital, RWTH Aachen, Aachen, Germany 
6  Department of Nuclear Medicine, University Hospital, RWTH Aachen, Aachen, Germany 
7  Institute of Radiochemistry and Experimental Molecular Imaging (IREMB), University Hospital of Cologne, Cologne, Germany 
8  Institute of Radiochemistry and Experimental Molecular Imaging (IREMB), University Hospital of Cologne, Cologne, Germany; Institute for Neuroscience and Medicine (INM-5), Nuclear Chemistry, Research Centre Jülich, Jülich, Germany 
9  Institute of Radiochemistry and Experimental Molecular Imaging (IREMB), University Hospital of Cologne, Cologne, Germany; Max Planck Institute for Metabolism Research, Cologne, Germany; Institute for Neuroscience and Medicine (INM-5), Nuclear Chemistry, Research Centre Jülich, Jülich, Germany 
10  Institute of Radiochemistry and Experimental Molecular Imaging (IREMB), University Hospital of Cologne, Cologne, Germany; Department of Nuclear Medicine, University Hospital, RWTH Aachen, Aachen, Germany 
Pages
1-7
Publication year
2018
Publication date
May 2018
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-018-25863-1
ProQuest document ID
2036773513
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.