MRI of inducible P-selectin expression in human activated platelets involved in the early stages of atherosclerosis

被引:42
作者
Jacobin-Valat, Marie-Josee [1 ]
Deramchia, Kamel [1 ]
Mornet, Stephane [2 ]
Hagemeyer, Christoph E. [3 ]
Bonetto, Stephane [1 ]
Robert, Remy [1 ]
Biran, Marc [1 ]
Massot, Philippe [1 ]
Miraux, Sylvain [1 ]
Sanchez, Stephane [1 ]
Bouzier-Sore, Anne-Karine [1 ]
Franconi, Jean-Michel [1 ]
Duguet, Etienne [2 ]
Clofent-Sanchez, Gisele [1 ]
机构
[1] Univ Bordeaux, CNRS, CRMSB, F-33076 Bordeaux, France
[2] Univ Bordeaux, CNRS, ICMCB, Pessac, France
[3] Baker IDI Heart & Diabet Inst, Atherothrombosis & Vasc Lab, Melbourne, Vic, Australia
关键词
molecular imaging; MRI contrast agents; atherosclerosis; nanoparticles; platelets; antibodies; P-selectin; SUPERPARAMAGNETIC IRON-OXIDE; CELL-ADHESION MOLECULE-1; TARGETED CONTRAST AGENT; IN-VIVO; HYPERLIPIDEMIC RABBITS; MAGNETIC NANOPARTICLES; ENDOTHELIAL-CELLS; PHAGE DISPLAY; INFLAMMATION; PLAQUES;
D O I
10.1002/nbm.1606
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
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 nano particles in the plaque. Our work provides support for the further assessment of the use of VH10-VUSPIO nano particles 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. Copyright (C) 2010 John Wiley & Sons, Ltd.
引用
收藏
页码:413 / 424
页数:12
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