| Imaging monocytes with iron oxide nanoparticles targeted towards the monocyte integrin MAC-1 (CD11b/CD18) does not result in improved atherosclerotic plaque detection by in vivo MRI. | |
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MedLine Citation:
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PMID: 20973112 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Imaging of macrophages with superparamagnetic iron oxide particles (SPIO) has been performed to improve detection of atherosclerotic plaque inflammation in human and mouse studies by molecular magnetic resonance imaging (MRI). Since affinity of the monocyte/macrophage integrin MAC-1 (CD11b/CD18) is upregulated in inflammation, we generated a contrast agent targeting CD11b (CD11b-SPIOs) for improved macrophage detection in plaques. CD11b-SPIOs and non-targeted SPIOs (control-SPIOs) were incubated in vitro with human monocytes/macrophages. As quantified by SPIO-induced MRI signal extinction, intracellular iron-content was significantly higher in monoytes/macrophages incubated with CD11b-SPIO than with control-SPIO in vitro (p < 0.05), suggesting an improved uptake of CD11b-SPIOs into monocytes. Therefore, the aortic arch (AA) and vessel branches of ApoE(-/-)-knockout mice on a Western-type diet were imaged before and 48 h after contrast agent injection of either CD11b-SPIOs or control-SPIOs, using a 9.4 T animal MRI system. The SPIO-induced change in the MRI signal was quantified, as well as the macrophage-content by anti-CD68 immunhistochemistry and the iron-content by Prussian-blue staining. However, SPIO-induced signal extinction in in vivo-MRI was similar in CD11b-SPIO and control-SPIO-injected animals, with a non-significant trend towards an improved uptake of CD11b-SPIOs in the subclavian artery and subsections of the AA. These data correlated well with the results obtained by histology. Although in vitro MRI-data indicated an increased uptake of targeted CD11b-SPIOs in monocytes/macrophages, in vivo mouse data do not allow improved atherosclerotic plaque detection compared WITH non-targeted SPIOs. Therefore, CD11b-targeted MRI contrast labelling of monocytes/macrophages does not seem to be a successful strategy in stable atherosclerotic plaques such as found in the ApoE(-/-)-knockout-model. However, the impressive correlation between MRI and histology data encourages further development of inflammation- and plaque-specific contrast agents for vulnerable plaque imaging. |
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Authors:
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C von zur Muhlen; A Fink-Petri; J Salaklang; D Paul; I Neudorfer; V Berti; A Merkle; K Peter; C Bode; D von Elverfeldt |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Contrast media & molecular imaging Volume: 5 ISSN: 1555-4317 ISO Abbreviation: Contrast Media Mol Imaging Publication Date: 2010 Sep-Oct |
Date Detail:
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Created Date: 2010-10-25 Completed Date: 2011-02-01 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101286760 Medline TA: Contrast Media Mol Imaging Country: United States |
Other Details:
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Languages: eng Pagination: 268-75 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 John Wiley & Sons, Ltd. |
Affiliation:
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Department of Cardiology and Angiology, University of Freiburg, Freiburg, Germany. constantin.vonzurmuehlen@uniklinik-freiburg.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, CD11b / chemistry* Apolipoproteins E / genetics Cells, Cultured Contrast Media / chemistry Ferric Compounds / chemistry* Humans Magnetic Resonance Imaging / methods* Mice Mice, Knockout Monocytes / cytology*, metabolism* Nanoparticles / chemistry* Plaque, Atherosclerotic / diagnosis*, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD11b; 0/Apolipoproteins E; 0/Contrast Media; 0/Ferric Compounds; 1309-37-1/ferric oxide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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