Near Infrared Fluorescence (NIRF) Molecular Imaging of Oxidized LDL with an Autoantibody in Experimental Atherosclerosis
Khamis, Ramzi Y
Woollard, Kevin J.
Hyde, Gareth D.
Boyle, Joseph J
Malik, Talat H
Granger, David W
Johnson, Jason L.
Matthews, Paul M
Haskard, Dorian ONote: Order does not necessarily reflect citation order of authors.
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CitationKhamis, R. Y., K. J. Woollard, G. D. Hyde, J. J. Boyle, C. Bicknell, S. Chang, T. H. Malik, et al. 2016. “Near Infrared Fluorescence (NIRF) Molecular Imaging of Oxidized LDL with an Autoantibody in Experimental Atherosclerosis.” Scientific Reports 6 (1): 21785. doi:10.1038/srep21785. http://dx.doi.org/10.1038/srep21785.
AbstractWe 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.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:26318625
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