Journal
MOLECULAR IMAGING
Volume 5, Issue 2, Pages 85-92Publisher
B C DECKER INC
DOI: 10.2310/7290.2006.00009
Keywords
atherosclerosis; MRI; fluorescence; nanoparticles; inflammation
Funding
- NCI NIH HHS [P50-CA86355, R24-CA92782] Funding Source: Medline
- NHLBI NIH HHS [U01-HL080731] Funding Source: Medline
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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.
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