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Molecules 2015, 20(2), 2081-2099; doi:10.3390/molecules20022081

Evaluation of the Radiolabeled Boronic Acid-Based FAP Inhibitor MIP-1232 for Atherosclerotic Plaque Imaging

1
Department of Chemistry and Applied Bioscience of ETH Zurich, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland
2
Division of Cardiovascular Surgery, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland
3
Institute for Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 268, 8057 Zurich, Switzerland
4
Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen PSI, Switzerland
*
Author to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Received: 4 December 2014 / Revised: 29 December 2014 / Accepted: 20 January 2015 / Published: 27 January 2015
(This article belongs to the Section Medicinal Chemistry)
View Full-Text   |   Download PDF [4619 KB, uploaded 27 January 2015]   |  

Abstract

Research towards the non-invasive imaging of atherosclerotic plaques is of high clinical priority as early recognition of vulnerable plaques may reduce the incidence of cardiovascular events. The fibroblast activation protein alpha (FAP) was recently proposed as inflammation-induced protease involved in the process of plaque vulnerability. In this study, FAP mRNA and protein levels were investigated by quantitative polymerase chain reaction and immunohistochemistry, respectively, in human endarterectomized carotid plaques. A published boronic-acid based FAP inhibitor, MIP-1232, was synthetized and radiolabeled with iodine-125. The potential of this radiotracer to image plaques was evaluated by in vitro autoradiography with human carotid plaques. Specificity was assessed with a xenograft with high and one with low FAP level, grown in mice. Target expression analyses revealed a moderately higher protein level in atherosclerotic plaques than normal arteries correlating with plaque vulnerability. No difference in expression was determined on mRNA level. The radiotracer was successfully produced and accumulated strongly in the FAP-positive SK-Mel-187 melanoma xenograft in vitro while accumulation was negligible in an NCI-H69 xenograft with low FAP levels. Binding of the tracer to endarterectomized tissue was similar in plaques and normal arteries, hampering its use for atherosclerosis imaging. View Full-Text
Keywords: atherosclerosis; fibroblast activation protein; carotid artery plaque; boronic acid-based inhibitor atherosclerosis; fibroblast activation protein; carotid artery plaque; boronic acid-based inhibitor
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Meletta, R.; Müller Herde, A.; Chiotellis, A.; Isa, M.; Rancic, Z.; Borel, N.; Ametamey, S.M.; Krämer, S.D.; Schibli, R. Evaluation of the Radiolabeled Boronic Acid-Based FAP Inhibitor MIP-1232 for Atherosclerotic Plaque Imaging. Molecules 2015, 20, 2081-2099.

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