A002 A tyrosine PEG-micelle magnetic resonance contrast agent for the detection of lipid rich areas in the atherosclerotic plaque

Vulnerable or high-risk atherosclerotic plaques often exhibit large lipid cores and thin fibrous caps that can lead to deadly vascular events via their rupture. In this study, PEGmicelles that incorporate a 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 target the lipid rich areas of atherosclerotic plaque in a highly efficient manner.These micelles were applied to apolipoprotein E -/- mice as a model of atherosclerosis. The abdominal aortas of the animals were imaged using T1-weighted highresolution MRI at 9.4 T before and up to 48hours 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 24hours postinjection 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 targeting approach, we demonstrated that lipid-rich areas in atherosclerotic plaque of ApoE -/- mice can be detected by MRI using Gd-DTPA micelles