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Tyrosine polyethylene glycol (PEG)‐micelle magnetic resonance contrast agent for the detection of lipid rich areas in atherosclerotic plaque
Author(s) -
Beilvert Anne,
Cormode David P.,
Chaubet Frédéric,
BrileySaebo Karen C.,
Mani Venkatesh,
Mulder Willem J.M.,
Vucic Esad,
Toussaint JeanFrançois,
Letourneur Didier,
Fayad Zahi A.
Publication year - 2009
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.22103
Subject(s) - micelle , polyethylene glycol , peg ratio , chemistry , magnetic resonance imaging , gadolinium , mri contrast agent , nuclear magnetic resonance , biochemistry , medicine , radiology , organic chemistry , finance , aqueous solution , economics , physics
Vulnerable or high‐risk atherosclerotic plaques often exhibit large lipid cores and thin fibrous caps that can lead to deadly vascular events when they rupture. In this study, polyethylene glycol (PEG)‐micelles that incorporate a gadolinium diethylenetriamine pentaacetic acid (Gd‐DTPA) amphiphile were used as an MR contrast agent. In an approach inspired by lipoproteins, the micelles were functionalized with tyrosine residues, an aromatic, lipophilic amino acid, to reach the lipid‐rich areas of atherosclerotic plaque in a highly efficient manner. These micelles were applied to apolipoprotein E −/− (ApoE −/− ) mice as a model of atherosclerosis. The abdominal aortas of the animals were imaged using T 1 ‐weighted ( T 1 W) high‐resolution MRI at 9.4T before and up to 48 h after the administration of the micelles. PEG‐micelles modified with 15% tyrosine residues yielded a significant enhancement of the abdominal aortic wall at 6 and 24 h postinjection (pi) as compared to unmodified micelles. Fluorescence microscopy on histological sections of the abdominal aorta showed a correlation between lipid‐rich areas and the distribution of the functionalized contrast agent in plaque. Using a simple approach, we demonstrated that lipid‐rich areas in atherosclerotic plaque of ApoE −/− mice can be detected by MRI using Gd‐DTPA micelles. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.