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

Khamis RY, Woollard KJ, Hyde GD, Boyle JJ, Bicknell C, Chang SH, Malik TH, Hara T, Mauskapf A, Granger DW, Johnson JL, Ntziachristos V, Matthews PM, Jaffer FA, Haskard DO (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 6

Article Number: 21785

DOI: 10.1038/srep21785

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.

Involved external institutions

Imperial College London / The Imperial College of Science, Technology and Medicine GB United Kingdom (GB) Harvard University US United States (USA) (US) GlaxoSmithKline plc. (GSK) GB United Kingdom (GB) University of Bristol GB United Kingdom (GB)

How to cite

APA:

Khamis, R.Y., Woollard, K.J., Hyde, G.D., Boyle, J.J., Bicknell, C., Chang, S.-H.,... Haskard, D.O. (2016). Near Infrared Fluorescence (NIRF) Molecular Imaging of Oxidized LDL with an Autoantibody in Experimental Atherosclerosis. Scientific Reports, 6. https://dx.doi.org/10.1038/srep21785

MLA:

Khamis, Ramzi Y., et al. "Near Infrared Fluorescence (NIRF) Molecular Imaging of Oxidized LDL with an Autoantibody in Experimental Atherosclerosis." Scientific Reports 6 (2016).

BibTeX: Download