Open AccessCellular Imaging of Inflammation in Atherosclerosis Using Magnetofluorescent Nanomaterials
Author(s) -
Farouc A. Jaffer,
Matthias Nahrendorf,
David E. Sosnovik,
Kimberly A. Kelly,
Elena Aikawa,
Ralph Weissleder
Publication year - 2006
Publication title -
molecular imaging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.815
H-Index - 60
eISSN - 1536-0121
pISSN - 1535-3508
DOI - 10.2310/7290.2006.00009
Subject(s) - in vivo , inflammation , ex vivo , atheroma , preclinical imaging , fluorescence lifetime imaging microscopy , fluorescence microscope , in vitro , pathology , macrophage , magnetic resonance imaging , chemistry , microbiology and biotechnology , biology , medicine , fluorescence , immunology , biochemistry , physics , radiology , quantum mechanics
Objective: Magnetofluorescent nanoparticles (MFNPs) offer the ability to image cellular inflammation in vivo. To better understand their cellular targeting and imaging capabilities in atherosclerosis, we investigated prototypical dextran-coated near-infrared fluorescent MFNPs in the apolipoprotein E-deficient (apo E−/−) mouse model. Methods and Results: In vitro MFNP uptake was highest in activated murine macrophages (p < .001). Apo E−/− mice (n = 11) were next injected with the MFNP (15 mg/kg iron) or saline. In vivo magnetic resonance imaging (MRI) demonstrated strong plaque enhancement by the MFNPs (p < .001 vs. saline), which was confirmed by multimodality ex vivo MRI and fluorescence reflectance imaging. On fluorescence microscopy, MFNPs were found in cellular-rich areas of atheroma and colocalized with immunofluorescent macrophages over endothelial cells and smooth muscle cells (p < .001). Conclusions: Here we show that (1) the in vitro and in vivo cellular distribution of atherosclerosis-targeted MFNPs can be quantified by using fluorescence imaging methods; (2) in atherosclerosis, dextranated MFNPs preferentially target macrophages; and (3) MFNP deposition in murine atheroma can be noninvasively detected by in vivo MRI. This study thus provides a foundation for using MFNPs to image genetic and/or pharmacological perturbations of cellular inflammation in experimental atherosclerosis and for the future development of novel targeted nanomaterials for atherosclerosis