Tyrosine polyethylene glycol (PEG)-micelle magnetic resonance contrast agent for the detection of lipid rich areas in atherosclerotic plaque

Authors

  • Anne Beilvert,

    1. INSERM U698, Cardiovascular Bioengineering, CHU X. Bichat, University Paris 7, Paris, France
    2. Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York, New York, USA
    3. BPC, Institut Galilée, University Paris 13, Villetaneuse, France
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  • David P. Cormode,

    1. Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York, New York, USA
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  • Frédéric Chaubet,

    1. INSERM U698, Cardiovascular Bioengineering, CHU X. Bichat, University Paris 7, Paris, France
    2. BPC, Institut Galilée, University Paris 13, Villetaneuse, France
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  • Karen C. Briley-Saebo,

    1. Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York, New York, USA
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  • Venkatesh Mani,

    1. Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York, New York, USA
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  • Willem J.M. Mulder,

    1. Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York, New York, USA
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  • Esad Vucic,

    1. Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York, New York, USA
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  • Jean-François Toussaint,

    1. Université Paris Descartes and INSERM U652, Pôle Imagerie et Explorations Fonctionnelles, Hôtel-Dieu, Paris, France
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  • Didier Letourneur,

    1. INSERM U698, Cardiovascular Bioengineering, CHU X. Bichat, University Paris 7, Paris, France
    2. BPC, Institut Galilée, University Paris 13, Villetaneuse, France
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  • Zahi A. Fayad

    Corresponding author
    1. Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York, New York, USA
    • Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1234, New York, NY 10029
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Abstract

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 T1-weighted (T1W) 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.

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