title: Near-infrared fluorescence imaging of murine atherosclerosis using an oxidized low density lipoprotein-targeted fluorochrome.
abstract: The aim of this study was to explore the feasibility of detecting plaques using an NIR797 fluorochrome-labeled, anti-oxLDL antibody (anti-oxLDL-NIR797) and near-infrared fluorescence (NIRF) imaging in a murine model of atherosclerosis. Anti-mouse oxLDL polyclonal antibodies were conjugated to NIR797 dyes to synthesis oxLDL-targeted NIRF probe. In situ and ex vivo NIRF imaging of the high-cholesterol diet-induced atherosclerotic lesions of apoE-/- mice (baseline) as well as ex vivo NIRF imaging in the progression and regression group (without or with atorvastatin treatment for another 8 weeks) were performed 24 h after an intravenous injection of 1 mg/kg of anti-oxLDL-NIR797, while phosphate-buffered saline (PBS) was used for the controls. The plaque areas were investigated using Oil Red O (ORO) staining. Aortas isolated from the apoE-/- mice 24 h post-injection exhibited a selective, strong, heterogeneous NIRF signal enhancement in the aortic root, arch, and bifurcation, whereas the PBS and competitive inhibition groups had limited NIRF signal changes (p < 0.05). There was a significant correlation between ORO staining and NIRF in the atherosclerotic aortas that received anti-oxLDL-NIR797. Immunofluorescence studies confirmed the colocalization of the oxLDL/macrophages and NIR797 fluorochromes. Furthermore, the atherosclerotic lesions of atorvastatin-treated mice showed reduced anti-oxLDL-NIR797 uptake and oxLDL expression. These results indicate that NIRF plaque imaging is feasible with an oxLDL-targeted NIRF probe. Thus, oxLDL-based molecular imaging of atherosclerotic plaques is feasible and may provide important methods for characterizing vulnerable plaques and monitoring the response to therapeutic interventions for atherosclerosis.
authors.affiliation: Department of Radiology, Zhongda Hospital, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, Jiangsu, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Lu
authors.forename: Song
authors.initials: S
authors.lastname: Wen
authors.forename: Ying
authors.initials: Y
authors.lastname: Cui
authors.forename: Sheng-Hong
authors.initials: SH
authors.lastname: Ju
authors.forename: King C
authors.initials: KC
authors.lastname: Li
authors.forename: Gao-Jun
authors.initials: GJ
authors.lastname: Teng
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism*; D001011:Aorta / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001018:Aortic Diseases / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000069059:Atorvastatin; D002460:Cell Line; D002791:Cholesterol, Dietary; D004195:Disease Models, Animal; D018450:Disease Progression; D005240:Feasibility Studies; D005456:Fluorescent Dyes / Q000378:metabolism*; D006538:Heptanoic Acids / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D017879:Isothiocyanates / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D061848:Optical Imaging; D058226:Plaque, Atherosclerotic; D011758:Pyrroles / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000906:Antibodies; D001057:Apolipoproteins E; D002791:Cholesterol, Dietary; D005456:Fluorescent Dyes; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017879:Isothiocyanates; D008077:Lipoproteins, LDL; D011758:Pyrroles; C099252:oxidized low density lipoprotein; D000069059:Atorvastatin