title: Evaluation of matrix metalloproteinases in atherosclerosis using a novel noninvasive imaging approach.
abstract: OBJECTIVE
  Despite great advances in our knowledge, atherosclerosis continues to kill more people than any other disease in the Western world. This is because our means of identifying truly vulnerable patients is limited. Prediction of atherosclerotic plaque rupture may be addressed by MRI of activated matrix metalloproteinases (MMPs), a family of enzymes that have been implicated in the vulnerability of plaques prone to rupture. This study evaluated the ability of the novel gadolinium-based MRI contrast agent P947 to target MMPs in atherosclerotic plaques.
  
  
  RESULTS
  The affinity of P947 toward activated MMPs was demonstrated in vitro. The affinity and specificity of P947 toward matrix metalloproteinase (MMP)-rich plaques was evaluated both in vivo using ApoE-/- mice and ex vivo in hyperlipidemic rabbits. Gadolinium content quantification and MRI showed a preferential accumulation of P947 in atherosclerotic lesions compared with the nontargeted reference compound, Gd-DOTA. The ex vivo assay on rabbit plaques revealed a higher uptake of P947. Moreover, using human carotid artery endarterectomy specimens, P947 facilitated discrimination between histologically defined MMP-rich and MMP-poor plaques. An in vivo MRI investigation in mice revealed that P947 greatly improved the ability to visualize and delineate atherosclerotic plaques.
  
  
  CONCLUSIONS
  P947 may be a useful tool for the detection and characterization of the MMP-rich atherosclerotic plaques.
authors.affiliation: Department of Radiology, the Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai School of Medicine, Box 1234, One Gustave L. Levy Place, New York, NY 10029, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Lancelot
authors.forename: Vardan
authors.initials: V
authors.lastname: Amirbekian
authors.forename: Irène
authors.initials: I
authors.lastname: Brigger
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Raynaud
authors.forename: Sébastien
authors.initials: S
authors.lastname: Ballet
authors.forename: Christelle
authors.initials: C
authors.lastname: David
authors.forename: Olivier
authors.initials: O
authors.lastname: Rousseaux
authors.forename: Soizic
authors.initials: S
authors.lastname: Le Greneur
authors.forename: Marc
authors.initials: M
authors.lastname: Port
authors.forename: Henri R
authors.initials: HR
authors.lastname: Lijnen
authors.forename: Patrick
authors.initials: P
authors.lastname: Bruneval
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Michel
authors.forename: Tanja
authors.initials: T
authors.lastname: Ouimet
authors.forename: Bernard
authors.initials: B
authors.lastname: Roques
authors.forename: Smbat
authors.initials: S
authors.lastname: Amirbekian
authors.forename: Fabien
authors.initials: F
authors.lastname: Hyafil
authors.forename: Esad
authors.initials: E
authors.lastname: Vucic
authors.forename: Juan Gilberto S
authors.initials: JG
authors.lastname: Aguinaldo
authors.forename: Claire
authors.initials: C
authors.lastname: Corot
authors.forename: Zahi A
authors.initials: ZA
authors.lastname: Fayad
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology*; D001057:Apolipoproteins E / Q000494:pharmacology; D050197:Atherosclerosis / Q000175:diagnosis*; D015415:Biomarkers / Q000032:analysis; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology*; D003287:Contrast Media; D004195:Disease Models, Animal; D005682:Gadolinium; D006801:Humans; D066298:In Vitro Techniques; D008279:Magnetic Resonance Imaging / Q000379:methods*; D020782:Matrix Metalloproteinases / Q000032:analysis / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011336:Probability; D011817:Rabbits; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D003287:Contrast Media; D005682:Gadolinium; D020782:Matrix Metalloproteinases