dc.contributor.author | Khamis, Ramzi Y | en_US |
dc.contributor.author | Woollard, Kevin J. | en_US |
dc.contributor.author | Hyde, Gareth D. | en_US |
dc.contributor.author | Boyle, Joseph J | en_US |
dc.contributor.author | Bicknell, Colin | en_US |
dc.contributor.author | Chang, Shang-Hung | en_US |
dc.contributor.author | Malik, Talat H | en_US |
dc.contributor.author | Hara, Tetsuya | en_US |
dc.contributor.author | Mauskapf, Adam | en_US |
dc.contributor.author | Granger, David W | en_US |
dc.contributor.author | Johnson, Jason L. | en_US |
dc.contributor.author | Ntziachristos, Vasilis | en_US |
dc.contributor.author | Matthews, Paul M | en_US |
dc.contributor.author | Jaffer, Farouc A | en_US |
dc.contributor.author | Haskard, Dorian O | en_US |
dc.date.accessioned | 2016-04-01T15:48:01Z | |
dc.date.issued | 2016 | en_US |
dc.identifier.citation | Khamis, 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.issn | 2045-2322 | en |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:26318625 | |
dc.description.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. | en |
dc.language.iso | en_US | en |
dc.publisher | Nature Publishing Group | en |
dc.relation.isversionof | doi:10.1038/srep21785 | en |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4766560/pdf/ | en |
dash.license | LAA | en_US |
dc.title | Near Infrared Fluorescence (NIRF) Molecular Imaging of Oxidized LDL with an Autoantibody in Experimental Atherosclerosis | en |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en |
dc.relation.journal | Scientific Reports | en |
dash.depositing.author | Jaffer, Farouc A | en_US |
dc.date.available | 2016-04-01T15:48:01Z | |
dc.identifier.doi | 10.1038/srep21785 | * |
dash.authorsordered | false | |
dash.contributor.affiliated | Jaffer, Farouc | |