Document Detail


Targeted iron oxide particles for in vivo magnetic resonance detection of atherosclerotic lesions with antibodies directed to oxidation-specific epitopes.
MedLine Citation:
PMID:  21106318     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: The aim of this study was to determine whether iron oxide particles targeted to oxidation-specific epitopes image atherosclerotic lesions.
BACKGROUND: Oxidized low-density lipoprotein plays a major role in atherosclerotic plaque progression and destabilization. Prior studies indicate that gadolinium micelles labeled with oxidation-specific antibodies allow for in vivo detection of vulnerable plaques with magnetic resonance imaging (MRI). However, issues related to biotransformation/retention of gadolinium might limit clinical translation. Iron oxides are recognized as safe and effective contrast agents for MRI. Because the efficacy of passively targeted iron particles remains variable, it was hypothesized that iron particles targeted to oxidation-specific epitopes might increase the utility of this platform.
METHODS: Lipid-coated ultra-small superparamagnetic iron particles (LUSPIOs) (<20 nm) and superparamagnetic iron particles (<40 nm) were conjugated with antibodies targeted to either malondialdehyde-lysine or oxidized phospholipid epitopes. All formulations were characterized, and their in vivo efficacy evaluated in apolipoprotein E deficient mice 24 h after bolus administration of a 3.9-mg Fe/kg dose with MRI. In vivo imaging data were correlated with the presence of oxidation-specific epitopes with immunohistochemistry.
RESULTS: MRI of atherosclerotic lesions, as manifested by signal loss, was observed after administration of targeted LUSPIOs. Immunohistochemistry confirmed the presence of malondialdehyde-epitopes and iron particles. Limited signal attenuation was observed for untargeted LUSPIOs. Additionally, no significant arterial wall uptake was observed for targeted or untargeted lipid-coated superparamagnetic iron oxide particles, due to their limited ability to penetrate the vessel wall.
CONCLUSIONS: This study demonstrates that LUSPIOs targeted to oxidation-specific epitopes image atherosclerotic lesions and suggests a clinically translatable platform for the detection of atherosclerotic plaque.
Authors:
Karen C Briley-Saebo; Young Seok Cho; Peter X Shaw; Sung Kee Ryu; Venkatesh Mani; Stephen Dickson; Ehsan Izadmehr; Simone Green; Zahi A Fayad; Sotirios Tsimikas
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-11-23
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  57     ISSN:  1558-3597     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-14     Completed Date:  2011-02-14     Revised Date:  2012-01-19    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  337-47     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Affiliation:
Translational and Molecular Imaging Institute, Department of Radiology, Mount Sinai School of Medicine, New York, New York, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies / administration & dosage,  diagnostic use*
Atherosclerosis / diagnosis*,  metabolism
Contrast Media / administration & dosage,  diagnostic use
Drug Delivery Systems / methods*
Epitopes / administration & dosage,  diagnostic use*,  immunology*
Ferric Compounds / administration & dosage,  diagnostic use*,  immunology*
Magnetic Resonance Imaging / methods*
Mice
Mice, Inbred C57BL
Mice, Knockout
Oxidation-Reduction
Particle Size
Grant Support
ID/Acronym/Agency:
R01 EB009638/EB/NIBIB NIH HHS; R01 EB009638-07/EB/NIBIB NIH HHS; R01 HL071021-07/HL/NHLBI NIH HHS; R01 HL078667-04S1/HL/NHLBI NIH HHS; R01 HL71021/HL/NHLBI NIH HHS; R01 HL78667/HL/NHLBI NIH HHS; R21 HL091399-01A2/HL/NHLBI NIH HHS; R21 HL091399-02/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies; 0/Contrast Media; 0/Epitopes; 0/Ferric Compounds; 1309-37-1/ferric oxide

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