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dc.contributor.authorKhamis, Ramzi Yen_US
dc.contributor.authorWoollard, Kevin J.en_US
dc.contributor.authorHyde, Gareth D.en_US
dc.contributor.authorBoyle, Joseph Jen_US
dc.contributor.authorBicknell, Colinen_US
dc.contributor.authorChang, Shang-Hungen_US
dc.contributor.authorMalik, Talat Hen_US
dc.contributor.authorHara, Tetsuyaen_US
dc.contributor.authorMauskapf, Adamen_US
dc.contributor.authorGranger, David Wen_US
dc.contributor.authorJohnson, Jason L.en_US
dc.contributor.authorNtziachristos, Vasilisen_US
dc.contributor.authorMatthews, Paul Men_US
dc.contributor.authorJaffer, Farouc Aen_US
dc.contributor.authorHaskard, Dorian Oen_US
dc.date.accessioned2016-04-01T15:48:01Z
dc.date.issued2016en_US
dc.identifier.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.en
dc.identifier.issn2045-2322en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:26318625
dc.description.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.en
dc.language.isoen_USen
dc.publisherNature Publishing Groupen
dc.relation.isversionofdoi:10.1038/srep21785en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4766560/pdf/en
dash.licenseLAAen_US
dc.titleNear Infrared Fluorescence (NIRF) Molecular Imaging of Oxidized LDL with an Autoantibody in Experimental Atherosclerosisen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalScientific Reportsen
dash.depositing.authorJaffer, Farouc Aen_US
dc.date.available2016-04-01T15:48:01Z
dc.identifier.doi10.1038/srep21785*
dash.authorsorderedfalse
dash.contributor.affiliatedJaffer, Farouc


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