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

Abstract : 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. Copyright © 2010 John Wiley & Sons, Ltd.
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Contributor : Stéphane Toulin <>
Submitted on : Friday, April 29, 2011 - 6:58:16 PM
Last modification on : Tuesday, June 23, 2020 - 10:32:02 AM

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Marie-Josée Jacobin-Valat, Kamel Deramchia, Stéphane Mornet, Christoph E Hagemeyer, Stéphane Bonetto, et al.. MRI of inducible P-selectin expression in human activated platelets involved in the early stages of atherosclerosis.. NMR in Biomedicine, Wiley, 2011, 24 (4), pp.413-424. ⟨10.1002/nbm.1606⟩. ⟨hal-00589664⟩



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