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

Magn Reson Med. 2009 Nov;62(5):1195-201. doi: 10.1002/mrm.22103.

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 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Abdominal / metabolism
  • Aorta, Abdominal / pathology
  • Atherosclerosis / diagnosis*
  • Atherosclerosis / metabolism*
  • Contrast Media / chemistry
  • Drug Carriers / chemistry*
  • Gadolinium DTPA* / chemistry
  • Image Enhancement / methods
  • Lipid Metabolism*
  • Magnetic Resonance Angiography / methods*
  • Mice
  • Mice, Knockout
  • Micelles
  • Polyethylene Glycols / chemistry*
  • Tyrosine / chemistry*

Substances

  • Contrast Media
  • Drug Carriers
  • Micelles
  • Polyethylene Glycols
  • Tyrosine
  • Gadolinium DTPA