Abstract 16462: Optical Molecular Imaging of Atheroma Inflammation With a Novel, Mannose Receptor Targeting Near-Infrared Fluorescence Probe in Genetically Engineered Mice and Atheromatous Rabbits
Background: Macrophage-rich atheroma is associated with the evolution and destabilization of plaques. In this study, we newly developed a near-infrared fluorescence (NIRF) optical molecular imaging probe targeting mannose receptor expressed on macrophages, and evaluated it in carotid artery of apoE knock-out mice, and in coronary sized vessels of atheromatous rabbits.
Methods and Results: A novel NIRF probe was fabricated by chemically conjugating glycol chitosan with mannose-PEG, cholesterol and NIRF dyes such as Cy5.5 (ext/emi 675/694 nm) for mouse imaging and Cy7 (ext/emi 743/767 nm) for rabbit imaging. In vitro, NIRF probe was selectively uptaken by RAW264.7 cells, and NIRF signals were estimated to be > 10-fold over control group (p<0.01). Plaque macrophage NIRF signals were prominently enhanced in carotid arteries of apoE -/- mice by multispectral laser confocal fluorescence imaging in vivo, and in coronary sized vessels of atheromatous rabbits by fluorescence reflectance imaging (Figure), which were induced by balloon induced endothelial denudation with a high-cholesterol diet for 12 weeks (vs. controls, p<0.01). Fluorescence microscopy and immunostaining of plaque sections demonstrated that augmented NIRF signals colocalized with macrophages in the atheromatous plaques.
Conclusions: Our newly developed mannose receptor targeting NIRF probe was able to selectively target and image macrophage-rich atheromata both in mouse arteries and in coronary sized rabbit vessels. This novel translatable molecular imaging approach will be useful as a potential tool for high-risk plaque imaging and screening ‘at risk’ patients.
- © 2013 by American Heart Association, Inc.