Abstract 3625: Targeted Ultra-Small Iron Oxide Particles for In Vivo MR Detection of Atherosclerotic Lesions Using Antibodies against Oxidized Low Density Lipoprotein

Abstract

Background: Oxidized low-density lipoprotein (OxLDL) plays a key role in the progression and destabilization of atherosclerotic plaque. Preliminary studies indicate that gadolinium (Gd) micelles labeled with oxidation-specific antibodies allow for specific targeting of vulnerable plaque. Due to issues associated with Gd toxicity (caused by retention and bio-transformation of the micelles), clinical translation of this platform may be limited. Iron oxides are recognized as safe and effective contrast agents for MRI. As a result, it was hypothesized that lipid coated ultra-small iron oxide particles (LUSPIOs) containing murine antibodies that bind malondialde-hyde lysine (MDA2) or oxidized phospholipids (EO6) associated with oxLDL may allow for the development of a safe platform for in vivo detection of vulnerable plaque. Materials and Results: Untargeted, MDA2, and EO6 labeled LUSPIOs were prepared and characterized with respect to efficacy, pharmacokinetics, and biodistribution in Apolipoprotein deficient mice (ApoE−/−). MRI was performed at 9.4T prior to and 24 hrs after LUSPIO administration (4 mg Fe/kg) using both gradient echo and positive contrast GRASP sequences. MDA2 and EO6 increased the particle size, blood half-life, and MR efficacy of the LUSPIOs, relative to untargeted particles. Only limited signal attenuation was observed following administration of untargeted LUSPIO. MRI and microscopy revealed that MDA2 and EO6 LUSPIOs accumulate within oxLDL rich foam cells (Fig.1 ). Conclusions: This study suggests that biocompatible LUSPIOs may provide a clinically translatable platform for the MR detection of oxLDL rich foam cells in humans. This research has received full or partial funding support from the American Heart Association, AHA National Center.