Detecting and assessing macrophages in vivo to evaluate atherosclerosis noninvasively using molecular MRI
We investigated the ability of targeted immunomicelles to detect and assess macrophages in atherosclerotic plaque using MRI in vivo. There is a large clinical need for a noninvasive tool to assess atherosclerosis from a molecular and cellular standpoint. Macrophages play a central role in atheroscle...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 104; no. 3; pp. 961 - 966 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences
16.01.2007
National Acad Sciences |
Subjects | |
Online Access | Get full text |
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Summary: | We investigated the ability of targeted immunomicelles to detect and assess macrophages in atherosclerotic plaque using MRI in vivo. There is a large clinical need for a noninvasive tool to assess atherosclerosis from a molecular and cellular standpoint. Macrophages play a central role in atherosclerosis and are associated with plaques vulnerable to rupture. Therefore, macrophage scavenger receptor (MSR) was chosen as a target for molecular MRI. MSR-targeted immunomicelles, micelles, and gadolinium-diethyltriaminepentaacetic acid (DTPA) were tested in ApoE-/- and WT mice by using in vivo MRI. Confocal laser-scanning microscopy colocalization, macrophage immunostaining and MRI correlation, competitive inhibition, and various other analyses were performed. In vivo MRI revealed that at 24 h postinjection, immunomicelles provided a 79% increase in signal intensity of atherosclerotic aortas in ApoE-/- mice compared with only 34% using untargeted micelles and no enhancement using gadolinium-DTPA. Confocal laser-scanning microscopy revealed colocalization between fluorescent immunomicelles and macrophages in plaques. There was a strong correlation between macrophage content in atherosclerotic plaques and the matched in vivo MRI results as measured by the percent normalized enhancement ratio. Monoclonal antibodies to MSR were able to significantly hinder immunomicelles from providing contrast enhancement of atherosclerotic vessels in vivo. Immunomicelles provided excellent validated in vivo enhancement of atherosclerotic plaques. The enhancement seen is related to the macrophage content of the atherosclerotic vessel areas imaged. Immunomicelles may aid in the detection of high macrophage content associated with plaques vulnerable to rupture. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 Author contributions: V.A., M.J.L., S.A., E.A.F., and Z.A.F. designed research; V.A., K.C.B.-S., S.A., J.G.S.A., D.B.W., E.V., J.C.F., and F.H. performed research; K.C.B.-S. and J.C.F. contributed new reagents/analytic tools; V.A., M.J.L., S.A., J.G.S.A., D.B.W., E.V., F.H., and V.M. analyzed data; and V.A., S.A., E.A.F., and Z.A.F. wrote the paper. Edited by Jan L. Breslow, The Rockefeller University, New York, NY, and approved November 16, 2006 |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.0606281104 |