Scavenger Receptor-AI–Targeted Iron Oxide Nanoparticles for In Vivo MRI Detection of Atherosclerotic Lesions
Objective—In search of molecular imaging modalities for specific detection of inflammatory atherosclerotic plaques, we explored the potential of targeting scavenger receptor-AI (SR-AI), which is highly expressed by lesional macrophages and linked to effective internalization machinery.
Approach and Results—Iron oxide–based ultrasmall superparamagnetic iron oxide (USPIO) was conjugated to a peptidic SR-AI ligand (0.371 mol Fe/L and 0.018 mol PP1/L). In vitro incubation of human or murine macrophages with SR-AI–targeted USPIO led to significantly higher iron uptake in vitro than with nontargeted USPIO, as judged by quantitative atomic absorption spectroscopy and Perl’s staining. Incremental uptake was strictly mediated by SRs. SR-AI–targeted USPIO displayed accelerated plasma decay and a 3.5-fold increase (P=0.01) in atherosclerotic plaque accumulation on intravenous injection into apolipoprotein E–deficient mice compared with nontargeted USPIO. In keeping, atherosclerotic humanized LDLr−/− chimeras with leukocyte expression of human SR-AI showed a significant improvement in contrast-to-noise ratio (2.7-fold; P=0.003) in the atherosclerotic aortic arch plaques 24 hours after injection of SR-AI–targeted USPIO compared with chimeras with leukocyte SR-AI deficiency.
Conclusions—Collectively, our data provide several lines of evidence that SR-AI–targeted molecular imaging of USPIO-based contrast agents holds great promise for in situ detection of inflammatory plaques in manifest atherosclerosis.
- molecular imaging
- magnetic resonance imaging
- receptors, scavenger
- ultrasmall superparamagnetic iron oxide
- Received October 25, 2012.
- Accepted May 16, 2013.
- © 2013 American Heart Association, Inc.