Abstract 17092: Intravascular Integrated OCT/NIRF Molecular Imaging with a Novel Mannose Receptor Targeting NIRF Probe to Identify Macrophage-rich High-Risk Plaques

Abstract

Background: Macrophage-rich active inflammatory plaques are at high-risk associated with acute coronary events. In current study, we newly developed a near-infrared fluorescence (NIRF) probe targeting mannose receptors which are expressed on plaque macrophages, and combined it with a fully integrated OCT (optical coherence tomography)/NIRF structural-molecular imaging to identify macrophage-rich high-risk plaques in coronary-sized vessels.

Methods and Results: A novel mannose receptor targeting probe was synthesized by chemically conjugating thiolated glycol chitosan with mannose-PEG-maleimide, and then further labeled it with NIRF emitting cyanine7 (ex/em 750 and 773nm). I.V. injection of the NIRF-nanoprobe at a dose of 10 mg/kg into balloon injured rabbits fed with high cholesterol diet was done 48 hours prior to imaging. In vivo OCT/NIRF imaging was performed in the infrarenal aorta and iliac artery at a high pullback speed (20mm/sec) just under contrast flushing, followed by ex vivo fluorescence reflectance imaging (FRI). NIRF macrophage signals in vivo were simultaneously enhanced only in the plaque lesions of the rabbit arteries, which morphology was clearly identified by OCT imaging (figure). Both in vivo and ex vivo imaging demonstrated a significant correlation (TBR) (p<0.05). Fluorescence microscopy and immunohistochemical staining of the corresponding plaque sections showing enhanced NIRF signals revealed a good colocalization with macrophage subsets.

Conclusions: Mannose receptor targeting NIRF probe combined with a dual-modal OCT/NIRF catheter system was able to specifically image macrophage-rich high-risk plaques in vivo in coronary-sized rabbit arteries. This novel imaging approach could have the potential to assess active plaque inflammation and offer a new avenue to identify high-risk coronary plaques prone to rupture.