Near Infrared Fluorescence (NIRF) Molecular Imaging of Oxidized LDL with an Autoantibody in Experimental Atherosclerosis

Ramzi Y Khamis, Kevin J Woollard, Gareth D Hyde, Joseph Boyle, Colin Bicknell, Shang-Hung Chang, Talat H Malik, Tetsuya Hara, Adam Mauskapf, David W Granger, Jason L Johnson, Vasilis Ntziachristos, Paul M Matthews, Farouc A Jaffer, Dorian O Haskard

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

We aimed to develop a quantitative antibody-based near infrared fluorescence (NIRF) approach for the imaging of oxidized LDL in atherosclerosis. LO1, a well- characterized monoclonal autoantibody that reacts with malondialdehyde-conjugated LDL, was labeled with a NIRF dye to yield LO1-750. LO1-750 specifically identified necrotic core in ex vivo human coronary lesions. Injection of LO1-750 into high fat (HF) fed atherosclerotic Ldlr−/− mice led to specific focal localization within the aortic arch and its branches, as detected by fluorescence molecular tomography (FMT) combined with micro-computed tomography (CT). Ex vivo confocal microscopy confirmed LO1-750 subendothelial localization of LO1-750 at sites of atherosclerosis, in the vicinity of macrophages. When compared with a NIRF reporter of MMP activity (MMPSense-645-FAST), both probes produced statistically significant increases in NIRF signal in the Ldlr−/− model in relation to duration of HF diet. Upon withdrawing the HF diet, the reduction in oxLDL accumulation, as demonstrated with LO1-750, was less marked than the effect seen on MMP activity. In the rabbit, in vivo injected LO1-750 localization was successfully imaged ex vivo in aortic lesions with a customised intra-arterial NIRF detection catheter. A partially humanized chimeric LO1-Fab-Cys localized similarly to the parent antibody in murine atheroma showing promise for future translation.
Original languageEnglish
Article number21785
Number of pages14
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 25 Feb 2016

Keywords

  • Applied immunology
  • Biological techniques
  • Biomarkers

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