Next Article in Journal
Metabolic Profiling of the Uncaria Hook Alkaloid Geissoschizine Methyl Ether in Rat and Human Liver Microsomes Using High-Performance Liquid Chromatography with Tandem Mass Spectrometry
Previous Article in Journal
Distinctive Anthocyanin Accumulation Responses to Temperature and Natural UV Radiation of Two Field-Grown Vitis vinifera L. Cultivars
Open AccessArticle

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
Molecules 2015, 20(2), 2081-2099; https://doi.org/10.3390/molecules20022081
Received: 4 December 2014 / Revised: 29 December 2014 / Accepted: 20 January 2015 / Published: 27 January 2015
(This article belongs to the Section Medicinal Chemistry)
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
Show Figures

Graphical abstract

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.

Show more citation formats Show less citations formats

Article Access Map by Country/Region

1
Only visits after 24 November 2015 are recorded.
Back to TopTop