CNRS, Université de Bordeaux, CRMSB, Bordeaux, France.
NMR Biomed. 2011 May;24(4):413-24. doi: 10.1002/nbm.1606. Epub 2010 Dec 29.
The noninvasive imaging of atherosclerotic plaques at an early stage of atherogenesis remains a major challenge for the evaluation of the pathologic state of patients at high risk of acute coronary syndromes. Recent studies have emphasized the importance of platelet-endothelial cell interactions in atherosclerosis-prone arteries at early stages, and the prominent role of P-selectin in the initial loose contact between platelets and diseased vessel walls. A specific MR contrast agent was developed here for the targeting, with high affinity, of P-selectin expressed in large amounts on activated platelets and endothelial cells. For this purpose, PEGylated dextran/iron oxide nanoparticles [PEG, poly(ethylene glycol)], named versatile ultrasmall superparamagnetic iron oxide (VUSPIO) particles, labeled with rhodamine were coupled to an anti-human P-selectin antibody (VH10). Flow cytometry and microscopy experiments on human activated platelets were highly correlated with MRI (performed at 4.7 and 0.2 T), with a 50% signal decrease in T(2) and T(1) values corresponding to the strong labeling of activated vs resting platelets. The number of 1000 VH10-VUSPIO nanoparticles attained per activated platelet appeared to be optimal for the detection of hypo- and hyper-signals in the platelet pellet on T(2) - and T(1) -weighted MRI. Furthermore, in vivo imaging of atherosclerotic plaques in ApoE mice at 4.7 T showed a spatial resolution adapted to the imaging of intimal thickening and a hypo-signal at 4.7 T, as a result of the accumulation of VH10-VUSPIO nanoparticles in the plaque. Our work provides support for the further assessment of the use of VH10-VUSPIO nanoparticles as a promising imaging modality able to identify the early stages of atherosclerosis with regard to the pertinence of both the target and the antibody-conjugated contrast agent used.
在动脉粥样硬化发生的早期阶段，对易发生急性冠脉综合征的高危患者的病理状态进行非侵入性成像仍然是一个主要挑战。最近的研究强调了血小板-内皮细胞相互作用在动脉粥样硬化易发生的早期阶段的重要性，以及 P-选择素在血小板与病变血管壁最初疏松接触中的突出作用。这里开发了一种特定的磁共振对比剂，用于靶向大量表达在活化血小板和内皮细胞上的 P-选择素，具有高亲和力。为此，将 PEG 化葡聚糖/氧化铁纳米颗粒[PEG，聚（乙二醇）]标记为 rhodamine，并偶联到抗人 P-选择素抗体（VH10）上，命名为多功能超小超顺磁性氧化铁（VUSPIO）颗粒。在人活化血小板上进行的流式细胞术和显微镜实验与 MRI 高度相关（在 4.7 和 0.2 T 下进行），T2 和 T1 值的信号降低 50%，对应于活化血小板与静止血小板的强烈标记。每个活化血小板上的 1000 个 VH10-VUSPIO 纳米颗粒的数量似乎是检测血小板颗粒中低信号和高信号的最佳数量，在 T2 和 T1 加权 MRI 上。此外，在 4.7 T 下对 ApoE 小鼠的动脉粥样硬化斑块进行体内成像显示，空间分辨率适合于成像内膜增厚，并且由于 VH10-VUSPIO 纳米颗粒在斑块中的积累，在 4.7 T 下呈现低信号。我们的工作为进一步评估 VH10-VUSPIO 纳米颗粒作为一种有前途的成像方式提供了支持，这种方式能够识别与所使用的靶标和抗体偶联对比剂的相关性都相关的动脉粥样硬化的早期阶段。
