Detecting and assessing macrophages in vivo to evaluate atherosclerosis
noninvasively using molecular MRI.
Authors Amirbekian V, Lipinski MJ, Briley-Saebo KC, Amirbekian S, Aguinaldo JG, Weinreb
DB, Vucic E, Frias JC, Hyafil F, Mani V, Fisher EA, Fayad ZA
Submitted By Submitted Externally on 3/4/2015
Status Published
Journal Proceedings of the National Academy of Sciences of the United States of America
Year 2007
Date Published 1/16/2007
Volume : Pages 104 : 961 - 966
PubMed Reference 17215360
Abstract 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

Investigators with authorship
Edward FisherNew York University School of Medicine