Indocyanine green enables near-infrared fluorescence imaging of lipid-rich, inflamed atherosclerotic plaques

• Published in: Science translational medicine Vol. 3; no. 84; p. 84ra45
• Main Authors: Vinegoni, Claudio, Botnaru, Ion, Aikawa, Elena, Calfon, Marcella A, Iwamoto, Yoshiko, Folco, Eduardo J, Ntziachristos, Vasilis, Weissleder, Ralph, Libby, Peter, Jaffer, Farouc A
• Format: Journal Article
• Language: English
• Published: United States 25.05.2011
• Subjects: Acetylation; Animals; Arteries - pathology; Arteries - physiopathology; Capillary Permeability - physiology; Cattle; Diagnostic Imaging - methods; Endocytosis; Fluorescence; Humans; Indocyanine Green; Inflammation - complications; Inflammation - pathology; Lipids - chemistry; Lipoproteins, LDL - metabolism; Macrophages - metabolism; Macrophages - pathology; Plaque, Atherosclerotic - complications; Plaque, Atherosclerotic - diagnosis; Plaque, Atherosclerotic - diagnostic imaging; Plaque, Atherosclerotic - physiopathology; Rabbits; Radiography; Serum Albumin, Bovine - metabolism; Spectroscopy, Near-Infrared - methods
• ISSN: 1946-6242
• DOI: 10.1126/scitranslmed.3001577

New high-resolution molecular and structural imaging strategies are needed to visualize high-risk plaques that are likely to cause acute myocardial infarction, because current diagnostic methods do not reliably identify at-risk subjects. Although molecular imaging agents are available for low-resolution detection of atherosclerosis in large arteries, a lack of imaging agents coupled to high-resolution modalities has limited molecular imaging of atherosclerosis in the smaller coronary arteries. Here, we have demonstrated that indocyanine green (ICG), a Food and Drug Administration-approved near-infrared fluorescence (NIRF)-emitting compound, targets atheromas within 20 min of injection and provides sufficient signal enhancement for in vivo detection of lipid-rich, inflamed, coronary-sized plaques in atherosclerotic rabbits. In vivo NIRF sensing was achieved with an intravascular wire in the aorta, a vessel of comparable caliber to human coronary arteries. Ex vivo fluorescence reflectance imaging showed high plaque target-to-background ratios in atheroma-bearing rabbits injected with ICG compared to atheroma-bearing rabbits injected with saline. In vitro studies using human macrophages established that ICG preferentially targets lipid-loaded macrophages. In an early clinical study of human atheroma specimens from four patients, we found that ICG colocalized with plaque macrophages and lipids. The atheroma-targeting capability of ICG has the potential to accelerate the clinical development of NIRF molecular imaging of high-risk plaques in humans.