TY - JOUR AB - We aimed to develop a quantitative antibody-based near infrared fluorescence (NIRF) approachfor the imaging of oxidized LDL in atherosclerosis. LO1, a well- characterized monoclonalautoantibody that reacts with malondialdehyde-conjugated LDL, was labeled with a NIRF dye toyield 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 focallocalization within the aortic arch and its branches, as detected by fluorescence moleculartomography (FMT) combined with micro-computed tomography (CT). Ex vivo confocalmicroscopy confirmed LO1-750 subendothelial localization of LO1-750 at sites ofatherosclerosis, in the vicinity of macrophages. When compared with a NIRF reporter of MMPactivity (MMPSense-645-FAST), both probes produced statistically significant increases inNIRF signal in the Ldlr-/- model in relation to duration of HF diet. When withdrawing the HFdiet, the reduction in oxLDL accumulation, as demonstrated with LO1-750, was less markedthan the effect seen on MMP activity. In the rabbit, in vivo injected LO1-750 localization wassuccessfully imaged ex vivo in aortic lesions with a customised intra-arterial NIRF detectioncatheter. A partially humanized chimeric LO1-Fab-Cys localized similarly to the parentantibody in murine atheroma showing promise for future translation. AU - Khamis,RY AU - Woollard,KJ AU - Hyde,GD AU - Boyle,JJ AU - Bicknell,C AU - Chang,S-H AU - Malik,TH AU - Hara,T AU - Mauskapf,A AU - Granger,DW AU - Johnson,JL AU - Ntziachristos,V AU - Matthews,PM AU - Jaffer,FA AU - Haskard,DO DO - 10.1038/srep21785 PY - 2016/// SN - 2045-2322 TI - Near Infrared Fluorescence (NIRF) Molecular Imaging of Oxidized LDL with an Autoantibody in Experimental Atherosclerosis T2 - Scientific Reports UR - http://dx.doi.org/10.1038/srep21785 UR - http://hdl.handle.net/10044/1/29155 VL - 6 ER -