期刊
MAGNETIC RESONANCE IN MEDICINE
卷 62, 期 5, 页码 1195-1201出版社
WILEY
DOI: 10.1002/mrm.22103
关键词
atherosclerosis; contrast agent; MRI; lipid core; micelle
资金
- National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) [R01 HL71021, R01 HL078667]
- ATHIM Project, Medicen Ile-de-France
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 (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 62:1195-1201, 2009. (C) 2009 Wiley-Liss, Inc.
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