title: Imaging of oxidation-specific epitopes with targeted nanoparticles to detect high-risk atherosclerotic lesions: progress and future directions.
abstract: Oxidation-specific epitopes (OSE) within developing atherosclerotic lesions are key antigens that drive innate and adaptive immune responses in atherosclerosis, leading to chronic inflammation. Oxidized phospholipids and malondialdehyde-lysine epitopes are well-characterized OSE present in human atherosclerotic lesions, particularly in pathologically defined vulnerable plaques. Using murine and human OSE-specific antibodies as targeting agents, we have developed radionuclide and magnetic resonance based nanoparticles, containing gadolinium, manganese or lipid-coated ultrasmall superparamagnetic iron oxide, to non-invasively image OSE within experimental atherosclerotic lesions. These methods quantitate plaque burden, allow detection of lesion progression and regression, plaque stabilization, and accumulation of OSE within macrophage-rich areas of the artery wall, suggesting they detect the most active lesions. Future studies will focus on using "natural" antibodies, lipopeptides, and mimotopes for imaging applications. These approaches should enhance the clinical translation of this technique to image, monitor, evaluate efficacy of novel therapeutic agents, and guide optimal therapy of high-risk atherosclerotic lesions.
authors.affiliation: Department of Basic Science and Craniofacial Biology, New York University, New York, NY, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Briley-Saebo
authors.forename: Calvin
authors.initials: C
authors.lastname: Yeang
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Witztum
authors.forename: Sotirios
authors.initials: S
authors.lastname: Tsimikas
mesh_terms: D000818:Animals; D000906:Antibodies; D050197:Atherosclerosis / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D003287:Contrast Media; D004195:Disease Models, Animal; D018450:Disease Progression; D000939:Epitopes; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D050356:Lipid Metabolism; D008279:Magnetic Resonance Imaging; D057054:Molecular Imaging / Q000379:methods*; D053758:Nanoparticles; D018384:Oxidative Stress; D058226:Plaque, Atherosclerotic; D011237:Predictive Value of Tests; D011877:Radionuclide Imaging; D012307:Risk Factors
chemical_list: D000906:Antibodies; D015415:Biomarkers; D003287:Contrast Media; D000939:Epitopes; D018836:Inflammation Mediators