title: Evaluation of the radiolabeled boronic acid-based FAP inhibitor MIP-1232 for atherosclerotic plaque imaging.
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.
authors: Department of Chemistry and Applied Bioscience of ETH Zurich, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland. romana.meletta@pharma.ethz.ch.
authors: Romana
authors: R
authors: Meletta
authors: Department of Chemistry and Applied Bioscience of ETH Zurich, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland. adrienne.herde@pharma.ethz.ch.
authors: Adrienne
authors: A
authors: Müller Herde
authors: 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@pharma.ethz.ch.
authors: Aristeidis
authors: A
authors: Chiotellis
authors: Department of Chemistry and Applied Bioscience of ETH Zurich, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland. isam@student.ethz.ch.
authors: Malsor
authors: M
authors: Isa
authors: Division of Cardiovascular Surgery, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland. zoran.rancic@usz.ch.
authors: Zoran
authors: Z
authors: Rancic
authors: Institute for Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 268, 8057 Zurich, Switzerland. n.borel@access.uzh.ch.
authors: Nicole
authors: N
authors: Borel
authors: Department of Chemistry and Applied Bioscience of ETH Zurich, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland. simon.ametamey@pharma.ethz.ch.
authors: Simon M
authors: SM
authors: Ametamey
authors: Department of Chemistry and Applied Bioscience of ETH Zurich, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland. stefanie.kraemer@pharma.ethz.ch.
authors: Stefanie D
authors: SD
authors: Krämer
authors: 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@pharma.ethz.ch.
authors: Roger
authors: R
authors: Schibli
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000368:Aged; D000818:Animals; D001549:Benzamides / Q000493:pharmacokinetics; D001896:Boron Compounds / Q000493:pharmacokinetics; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging* / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D010450:Endopeptidases; D005260:Female; D018093:Gelatinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008546:Melanoma, Experimental / Q000000981:diagnostic imaging; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009368:Neoplasm Transplantation; D058226:Plaque, Atherosclerotic / Q000000981:diagnostic imaging* / Q000378:metabolism; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D000199:Actins; D001549:Benzamides; D001896:Boron Compounds; D010450:Endopeptidases; D018093:Gelatinases; D007457:Iodine Radioisotopes; D008565:Membrane Proteins; D019275:Radiopharmaceuticals; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha; C000601992:MIP-1232
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