Molecular Imaging of Oxidation-Specific Epitopes to Detect High-Risk Atherosclerotic Plaques

The oxidation of lipoproteins is a critical factor in the initiation, progression, and destabilization of atherosclerotic lesions. Reactive oxygen species and enzymes in the vessel wall modify lipoproteins to generate a variety of oxidation-specific epitopes (OSE). OSE are pro-inflammatory, immunogenic, and pro-atherogenic by activating macrophages leading to foam cell formation, apoptosis, and necrotic cores. OSE activate the innate and adaptive immune systems that lead to pro-inflammatory responses. The immunological properties of OSE have facilitated the generation and characterization and modification of murine and human monoclonal antibodies as imaging agents. Nuclear and magnetic resonance techniques have been used to visualize OSE in preclinical models. OSE-targeted antibodies have been derivatized with radioisotopes or complexed with gadolinium, manganese, and iron oxide nanoparticles to facilitate in vivo imaging of atherosclerotic lesions. OSE-targeted antibody uptake in the vessel wall is proportional to plaque burden in early and intermediate lesions allowing quantitation of the extent of atherosclerosis. In intervention studies, imaging of OSE allows the detection of atherosclerosis regression and features of plaque stabilization. Translation of these approaches to humans may provide sensitive techniques to image, diagnose, and monitor high-risk atherosclerotic lesions, guide optimal therapeutic interventions, and evaluate efficacy of novel therapeutic agents.