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

Research output: Contribution to journalArticleResearchpeer-review

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, Marie-Josee ; Deramchia, Kamel ; Mornet, Stephane ; Hagemeyer, Christoph Eugen ; Bonetto, Stephane ; Robert, Remy ; Biran, Marc ; Massot, Philippe ; Miraux, Sylvain ; Clofent-Sanchez, Gisele ; Bouzier-Sore, Anne-Karine ; Franconi, Jean-Michel ; Duguet, Etienne ; Sanchez, Stephane. / MRI of inducible P-selectin expression in human activated platelets involved in the early stages of atherosclerosis. In: NMR in Biomedicine. 2011 ; Vol. 24, No. 4. pp. 413 - 424.
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title = "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 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.",
author = "Marie-Josee Jacobin-Valat and Kamel Deramchia and Stephane Mornet and Hagemeyer, {Christoph Eugen} and Stephane Bonetto and Remy Robert and Marc Biran and Philippe Massot and Sylvain Miraux and Gisele Clofent-Sanchez and Anne-Karine Bouzier-Sore and Jean-Michel Franconi and Etienne Duguet and Stephane Sanchez",
year = "2011",
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Jacobin-Valat, M-J, Deramchia, K, Mornet, S, Hagemeyer, CE, 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, vol. 24, no. 4, pp. 413 - 424. https://doi.org/10.1002/nbm.1606

MRI of inducible P-selectin expression in human activated platelets involved in the early stages of atherosclerosis. / Jacobin-Valat, Marie-Josee; Deramchia, Kamel; Mornet, Stephane; Hagemeyer, Christoph Eugen; Bonetto, Stephane; Robert, Remy; Biran, Marc; Massot, Philippe; Miraux, Sylvain; Clofent-Sanchez, Gisele; Bouzier-Sore, Anne-Karine; Franconi, Jean-Michel; Duguet, Etienne; Sanchez, Stephane.

In: NMR in Biomedicine, Vol. 24, No. 4, 2011, p. 413 - 424.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - MRI of inducible P-selectin expression in human activated platelets involved in the early stages of atherosclerosis

AU - Jacobin-Valat, Marie-Josee

AU - Deramchia, Kamel

AU - Mornet, Stephane

AU - Hagemeyer, Christoph Eugen

AU - Bonetto, Stephane

AU - Robert, Remy

AU - Biran, Marc

AU - Massot, Philippe

AU - Miraux, Sylvain

AU - Clofent-Sanchez, Gisele

AU - Bouzier-Sore, Anne-Karine

AU - Franconi, Jean-Michel

AU - Duguet, Etienne

AU - Sanchez, Stephane

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

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