Abstract
Successful imaging of atherosclerosis, one of the leading global causes of death, is crucial for diagnosis and intervention. Near-infrared fluorescence (NIRF) imaging has been widely adopted along with multimodal/hybrid imaging systems for plaque detection. We evaluate two macrophage-targeting fluorescent tracers for NIRF imaging (TLR4-ZW800-1C and Feraheme-Alexa Fluor 750) in an atherosclerotic murine cohort, where the left carotid artery (LCA) is ligated to cause stenosis, and the right carotid artery (RCA) is used as a control. Imaging performed on dissected tissues revealed that both tracers had high uptake in the diseased vessel compared to the control, which was readily visible even at short exposure times. In addition, ZW800-1C’s renal clearance ability and Feraheme’s FDA approval puts these two tracers in line with other NIRF tracers such as ICG. Continued investigation with these tracers using intravascular NIRF imaging and larger animal models is warranted for clinical translation.
Highlights
The left carotid artery (LCA) of mice with plaque (T3–8, F1–6) were visibly thicker than the right carotid artery (RCA) due to the stenosis caused by the ligation, with a combined mean of a 38% increase in thickness (Table 1)
Since toll-like receptor 4 (TLR4) is involved in critical steps of plaque formation, and Feraheme is readily taken up by macrophages involved in the resulting inflammatory process, both fluorescent tracers show promise in being able to identify high-risk plaques likely to progress and can be included in the arsenal of molecular probes for Near-infrared fluorescence (NIRF) imaging of atherosclerosis [7]
A limitation of the study is that our NIRF imaging system is suited for whole-body rodent imaging, and we have not thoroughly investigated tuning the system for optimal noninvasive imaging
Summary
Cardiovascular disease remains the largest cause of mortality in the United States, accounting for about 860,000 deaths in 2017 [1]. Of these deaths, 42.6% were attributed to coronary heart disease paving the way for imaging research to detect the underlying atherosclerotic plaques for early diagnosis and intervention [1,2]. Successful imaging of vulnerable plaques involves determining their morphology and composition, the detection of an inflamed, thin-cap fibroatheroma (TCFA) featuring a lipidrich, atheromatous core, a thin fibrous cap with macrophage and lymphocyte infiltration, decreased smooth muscle cell content, and expansive arterial remodeling [3]
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