Tyrosine Polyethylene Glycol (PEG)-Micelle Magnetic Resonance Contrast Agent for the Detection of Lipid Rich Areas in Atherosclerotic Plaque
Tyrosine Polyethylene Glycol (PEG)-Micelle Magnetic Resonance Contrast Agent for the Detection of Lipid Rich Areas in Atherosclerotic Plaque
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DOI：
10.1002/mrm.22103
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发表时间：
2009-11-01
影响因子：
3.3
通讯作者：
Fayad, Zahi A.
中科院分区：
文献类型：
--
作者：
Beilvert, Anne;Cormode, David P.;Fayad, Zahi A.
脆弱或高危的动脉粥样硬化斑块通常表现出大的脂质核心和薄的纤维帽，当它们破裂时可能导致致命的血管事件。在这项研究中，聚乙二醇（PEG）胶束，纳入钆二亚乙基三胺五乙酸（Gd-DTPA）两亲物被用作MR造影剂。在一种受脂蛋白启发的方法中，胶束用酪氨酸残基（一种芳香族亲脂性氨基酸）官能化，以高效的方式到达动脉粥样硬化斑块的富含脂质的区域。将这些胶束应用于载脂蛋白E-/-（ApoE（-/-））小鼠作为动脉粥样硬化模型。在胶束给药前和给药后48 h内，使用9.4T的T1加权（T1 W）高分辨率MRI对动物的腹部肿块进行成像。与未修饰的胶束相比，用15%酪氨酸残基修饰的PEG胶束在注射后6和24小时（PI）产生了显着增强的腹主动脉壁。腹主动脉组织学切片的荧光显微镜检查显示脂质丰富的区域和斑块中功能化造影剂的分布之间存在相关性。使用一种简单的方法，我们证明了在ApoE（-/-）小鼠的动脉粥样硬化斑块中富含脂质的区域可以通过使用Gd-DTPA胶束的MRI检测。Magn Reson Med 62：1195-1201，2009。(C)2009威利-利斯公司
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.