Development of a Magnetic Resonance Imaging Protocol for the Characterization of Atherosclerotic Plaque by Using Vascular Cell Adhesion Molecule-1 and Apoptosis-Targeted Ultrasmall Superparamagnetic Iron Oxide Derivatives
Development of a Magnetic Resonance Imaging Protocol for the Characterization of Atherosclerotic Plaque by Using Vascular Cell Adhesion Molecule-1 and Apoptosis-Targeted Ultrasmall Superparamagnetic Iron Oxide Derivatives
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DOI：
10.1161/atvbaha.112.245415
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发表时间：
2012-06-01
影响因子：
8.7
通讯作者：
Muller, Robert N.
中科院分区：
文献类型：
--
作者：
Burtea, Carmen;Ballet, Sebastien;Muller, Robert N.
目的：急性缺血事件通常是由于富含脂质的斑块破裂引起的，而这些斑块在血管造影上往往是不可见的。将我们前期工作中研究的血管细胞黏附分子-1和凋亡细胞靶向多肽与超小超顺磁性氧化铁(USPIO-R832用于血管细胞黏附分子-1靶向；USPIO-R826用于细胞凋亡靶向)偶联，并进行磁共振成像。方法和结果：将载脂蛋白E基因敲除的小鼠注射0.1mmolFe/kg体重，在4.7-T Bruker磁共振成像仪上进行成像，直到造影剂注射后24小时。采集主动脉标本，进行组织化学检查，用ImageJ软件分析磁共振图像和组织学图像。USPIO-R832增强的斑块包含集中在斑块帽内的巨噬细胞和一个大的坏死核，而USPIO-R826对斑块内富含巨噬细胞和中性脂肪的斑块产生负增强。两种USPIO衍生物在组织切片上与它们的靶点共定位，并能够检测到具有脆弱形态的斑块，但每一种都检测到特定的环境。结论-我们的血管细胞黏附分子-1和针对凋亡细胞的USPIO衍生物似乎是非常有前途的动脉粥样硬化成像工具，有助于检测易损斑块。它们能够在低剂量下达到目标，并且在给药后30分钟内就能达到目标。(动脉血栓血管生物)2012；32：E36-48。)
Objective-Acute ischemic events are often caused by the disruption of lipid-rich plaques, which are frequently not angiographically visible. Vascular cell adhesion molecule-1 and apoptotic cell-targeted peptides studied during our previous work were conjugated to ultrasmall superparamagnetic iron oxide (USPIO) (USPIO-R832 for vascular cell adhesion molecule-1 targeting; USPIO-R826 for apoptosis targeting) and assessed by magnetic resonance imaging.Methods and Results-Apolipoprotein E knockout mice were injected with 0.1 mmol Fe/kg body weight and were imaged on a 4.7-T Bruker magnetic resonance imaging until 24 hours after contrast agent administration. Aortic samples were then harvested and examined by histochemistry, and the magnetic resonance images and histological micrographs were analyzed with ImageJ software. The plaques enhanced by USPIO-R832 contained macrophages concentrated in the cap and a large necrotic core, whereas USPIO-R826 produced a negative enhancement of plaques rich in macrophages and neutral fats concentrated inside the plaque. Both USPIO derivatives colocalized with their target on histological sections and were able to detect plaques with a vulnerable morphology, but each one is detecting a specific environment.Conclusion-Our vascular cell adhesion molecule-1 and apoptotic cell targeted USPIO derivatives seem to be highly promising tools for atherosclerosis imaging contributing to the detection of vulnerable plaques. They are able to attain their target in low doses and as fast as 30 minutes after administration. (Arterioscler Thromb Vasc Biol. 2012;32:e36-48.)