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

Marie-Josee Jacobin-Valat, Kamel Deramchia, Stephane Mornet, Christoph Eugen Hagemeyer, Stephane Bonetto, Remy Robert, Marc Biran, Philippe Massot, Sylvain Miraux, Gisele Clofent-Sanchez, Anne-Karine Bouzier-Sore, Jean-Michel Franconi, Etienne Duguet, Stephane Sanchez

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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 T2 and T1 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 T2- and T1-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.
Original languageEnglish
Pages (from-to)413 - 424
Number of pages12
JournalNMR in Biomedicine
Volume24
Issue number4
DOIs
Publication statusPublished - 2011
Externally publishedYes

Cite this

Jacobin-Valat, M-J., Deramchia, K., Mornet, S., Hagemeyer, C. E., Bonetto, S., Robert, R., Biran, M., Massot, P., Miraux, S., Clofent-Sanchez, G., Bouzier-Sore, A-K., Franconi, J-M., Duguet, E., & Sanchez, S. (2011). MRI of inducible P-selectin expression in human activated platelets involved in the early stages of atherosclerosis. NMR in Biomedicine, 24(4), 413 - 424. https://doi.org/10.1002/nbm.1606