Cited by 356Atherosclerosis and Cardiovascular DiseasesCardiac Imaging and DiagnosticsNanoparticle-Based Drug Delivery

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Detecting and assessing macrophages in vivo to evaluate atherosclerosis noninvasively using molecular MRI

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Amirbekian, Vardan, Lipinski, Michael J., Briley-Saebo, Karen C., Amirbekian, Smbat, Aguinaldo, Juan Gilberto S., Weinreb, David B., Vucic, Esad, Frias, Juan C., Hyafil, Fabien, Mani, Venkatesh, Fisher, Edward A., Fayad, Zahi A.·2007·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0606281104PMC PMC1766334

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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 rupture.

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Authors: Amirbekian, V., Lipinski, M. J., Briley-Saebo, K. C., Amirbekian, S., Aguinaldo, J. G. S., Weinreb, D. B., Vucic, E., Frias, J. C., Hyafil, F., Mani, V., Fisher, E. A., & Fayad, Z. A.
Affiliations: Johns Hopkins University (US)
Sarnoff Cardiovascular Research Foundation (US)
Icahn School of Medicine at Mount Sinai (US)
Emory University (US)
New York University (US)
ORCID: Briley-Saebo, Karen C.
Vucic, Esad
Frias, Juan C.
Hyafil, Fabien
Mani, Venkatesh
Fisher, Edward A.
Fayad, Zahi A.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2007-01-16
Volume: 104
Issue: 3
Pages: 961-966
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.0606281104
PMC: PMC1766334
OpenAlex: W1986805734
Cited by: 356
References: 35
Citations by year: 2026: 1 · 2025: 1 · 2024: 3 · 2023: 4 · 2022: 9 · 2021: 4 · 2020: 12 · 2019: 14 · 2018: 7 · 2017: 13 · 2016: 14 · 2015: 23 · 2014: 26 · 2013: 19 · 2012: 38
FWCI: 17.16
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Science Foundation (9724504, 1 S10 RR0 9145-01)
Sarnoff Cardiovascular Research Foundation
National Institutes of Health (1s10rr009145-01, 1S10 RR0 9145-01)
National Heart, Lung, and Blood Institute (R01HL078667, U01 HL 71021, R01HL071021, U01HL070524)
National Cancer Institute (R24CA095823)
National Center for Research Resources (1 S10RR0 9145-01)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Cardiac Imaging and Diagnostics
Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Keywords: atherosclerosis, macrophages, molecular MRI, macrophage scavenger receptor, targeted contrast agents, non-invasive imaging, atherosclerotic plaque, plaque vulnerability, ApoE-deficient mice, Gd-DTPA, monoclonal antibodies, macrophage content
MeSH terms: Animals, Apolipoproteins E, Macrophages, Magnetic Resonance Imaging, Micelles, Microscopy, Confocal, Atherosclerosis, Mice

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Detecting and assessing macrophages in vivo to evaluate atherosclerosis noninvasively using molecular MRI

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