Evaluation of the Radiolabeled Boronic Acid-Based FAP Inhibitor MIP-1232 for Atherosclerotic Plaque Imaging
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 involve...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2015-01-01
|
Series: | Molecules |
Subjects: | |
Online Access: | http://www.mdpi.com/1420-3049/20/2/2081 |
id |
doaj-ed397267dc974670a1aac82c56efd8fb |
---|---|
record_format |
Article |
spelling |
doaj-ed397267dc974670a1aac82c56efd8fb2020-11-25T02:46:15ZengMDPI AGMolecules1420-30492015-01-012022081209910.3390/molecules20022081molecules20022081Evaluation of the Radiolabeled Boronic Acid-Based FAP Inhibitor MIP-1232 for Atherosclerotic Plaque ImagingRomana Meletta0Adrienne Müller Herde1Aristeidis Chiotellis2Malsor Isa3Zoran Rancic4Nicole Borel5Simon M. Ametamey6Stefanie D. Krämer7Roger Schibli8Department of Chemistry and Applied Bioscience of ETH Zurich, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Vladimir-Prelog-Weg 4, 8093 Zurich, SwitzerlandDepartment of Chemistry and Applied Bioscience of ETH Zurich, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Vladimir-Prelog-Weg 4, 8093 Zurich, SwitzerlandDepartment of Chemistry and Applied Bioscience of ETH Zurich, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Vladimir-Prelog-Weg 4, 8093 Zurich, SwitzerlandDepartment of Chemistry and Applied Bioscience of ETH Zurich, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Vladimir-Prelog-Weg 4, 8093 Zurich, SwitzerlandDivision of Cardiovascular Surgery, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, SwitzerlandInstitute for Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 268, 8057 Zurich, SwitzerlandDepartment of Chemistry and Applied Bioscience of ETH Zurich, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Vladimir-Prelog-Weg 4, 8093 Zurich, SwitzerlandDepartment of Chemistry and Applied Bioscience of ETH Zurich, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Vladimir-Prelog-Weg 4, 8093 Zurich, SwitzerlandDepartment of Chemistry and Applied Bioscience of ETH Zurich, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Vladimir-Prelog-Weg 4, 8093 Zurich, SwitzerlandResearch 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.http://www.mdpi.com/1420-3049/20/2/2081atherosclerosisfibroblast activation proteincarotid artery plaqueboronic acid-based inhibitor |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Romana Meletta Adrienne Müller Herde Aristeidis Chiotellis Malsor Isa Zoran Rancic Nicole Borel Simon M. Ametamey Stefanie D. Krämer Roger Schibli |
spellingShingle |
Romana Meletta Adrienne Müller Herde Aristeidis Chiotellis Malsor Isa Zoran Rancic Nicole Borel Simon M. Ametamey Stefanie D. Krämer Roger Schibli Evaluation of the Radiolabeled Boronic Acid-Based FAP Inhibitor MIP-1232 for Atherosclerotic Plaque Imaging Molecules atherosclerosis fibroblast activation protein carotid artery plaque boronic acid-based inhibitor |
author_facet |
Romana Meletta Adrienne Müller Herde Aristeidis Chiotellis Malsor Isa Zoran Rancic Nicole Borel Simon M. Ametamey Stefanie D. Krämer Roger Schibli |
author_sort |
Romana Meletta |
title |
Evaluation of the Radiolabeled Boronic Acid-Based FAP Inhibitor MIP-1232 for Atherosclerotic Plaque Imaging |
title_short |
Evaluation of the Radiolabeled Boronic Acid-Based FAP Inhibitor MIP-1232 for Atherosclerotic Plaque Imaging |
title_full |
Evaluation of the Radiolabeled Boronic Acid-Based FAP Inhibitor MIP-1232 for Atherosclerotic Plaque Imaging |
title_fullStr |
Evaluation of the Radiolabeled Boronic Acid-Based FAP Inhibitor MIP-1232 for Atherosclerotic Plaque Imaging |
title_full_unstemmed |
Evaluation of the Radiolabeled Boronic Acid-Based FAP Inhibitor MIP-1232 for Atherosclerotic Plaque Imaging |
title_sort |
evaluation of the radiolabeled boronic acid-based fap inhibitor mip-1232 for atherosclerotic plaque imaging |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2015-01-01 |
description |
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. |
topic |
atherosclerosis fibroblast activation protein carotid artery plaque boronic acid-based inhibitor |
url |
http://www.mdpi.com/1420-3049/20/2/2081 |
work_keys_str_mv |
AT romanameletta evaluationoftheradiolabeledboronicacidbasedfapinhibitormip1232foratheroscleroticplaqueimaging AT adriennemullerherde evaluationoftheradiolabeledboronicacidbasedfapinhibitormip1232foratheroscleroticplaqueimaging AT aristeidischiotellis evaluationoftheradiolabeledboronicacidbasedfapinhibitormip1232foratheroscleroticplaqueimaging AT malsorisa evaluationoftheradiolabeledboronicacidbasedfapinhibitormip1232foratheroscleroticplaqueimaging AT zoranrancic evaluationoftheradiolabeledboronicacidbasedfapinhibitormip1232foratheroscleroticplaqueimaging AT nicoleborel evaluationoftheradiolabeledboronicacidbasedfapinhibitormip1232foratheroscleroticplaqueimaging AT simonmametamey evaluationoftheradiolabeledboronicacidbasedfapinhibitormip1232foratheroscleroticplaqueimaging AT stefaniedkramer evaluationoftheradiolabeledboronicacidbasedfapinhibitormip1232foratheroscleroticplaqueimaging AT rogerschibli evaluationoftheradiolabeledboronicacidbasedfapinhibitormip1232foratheroscleroticplaqueimaging |
_version_ |
1724759632465887232 |