Near-infrared fluorescence imaging of murine atherosclerosis using an oxidized low density lipoprotein-targeted fluorochrome

Tong Lu, Song Wen, Ying Cui, Sheng Hong Ju, King C. Li, Gao Jun Teng

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)221-231
Number of pages11
JournalInternational Journal of Cardiovascular Imaging
Volume30
Issue number1
DOIs
StatePublished - Jan 2014
Externally publishedYes

Keywords

  • Atherosclerosis
  • Inflammation
  • Near-infrared fluorescence imaging
  • oxLDL

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

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