Evaluation of the Radiolabeled Boronic Acid-Based FAP Inhibitor MIP-1232 for Atherosclerotic Plaque Imaging
Romana Meletta,
Adrienne Müller Herde,
Aristeidis Chiotellis,
Malsor Isa,
Zoran Rancic,
Nicole Borel,
Simon M. Ametamey,
Stefanie D. Krämer,
Roger Schibli
Affiliations
Romana Meletta
Department of Chemistry and Applied Bioscience of ETH Zurich, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland
Adrienne Müller Herde
Department of Chemistry and Applied Bioscience of ETH Zurich, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland
Aristeidis Chiotellis
Department of Chemistry and Applied Bioscience of ETH Zurich, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland
Malsor Isa
Department of Chemistry and Applied Bioscience of ETH Zurich, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland
Zoran Rancic
Division of Cardiovascular Surgery, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland
Nicole Borel
Institute for Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 268, 8057 Zurich, Switzerland
Simon M. Ametamey
Department of Chemistry and Applied Bioscience of ETH Zurich, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland
Stefanie D. Krämer
Department of Chemistry and Applied Bioscience of ETH Zurich, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland
Roger Schibli
Department of Chemistry and Applied Bioscience of ETH Zurich, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland
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.