Tyrosine polyethylene glycol (PEG)-micelle magnetic resonance contrast agent for the detection of lipid rich areas in atherosclerotic plaque.
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.
Beilvert
Anne
A
INSERM U698, Cardiovascular Bioengineering, CHU X. Bichat, University Paris 7, Paris, France.
Cormode
David P
DP
Chaubet
Frédéric
F
Briley-Saebo
Karen C
KC
Mani
Venkatesh
V
Mulder
Willem J M
WJ
Vucic
Esad
E
Toussaint
Jean-François
JF
Letourneur
Didier
D
Fayad
Zahi A
ZA
D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000175:diagnosis* / Q000378:metabolism*; D003287:Contrast Media / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D019786:Gadolinium DTPA / Q000737:chemistry; D007089:Image Enhancement / Q000379:methods; D050356:Lipid Metabolism; D018810:Magnetic Resonance Angiography / Q000379:methods*; D051379:Mice; D018345:Mice, Knockout; D008823:Micelles; D011092:Polyethylene Glycols / Q000737:chemistry*; D014443:Tyrosine / Q000737:chemistry*
D003287:Contrast Media; D004337:Drug Carriers; D008823:Micelles; D011092:Polyethylene Glycols; D014443:Tyrosine; D019786:Gadolinium DTPA