Imperial College London
Alternate

Dr Joseph J Boyle

Faculty of Medicine, National Heart & Lung Institute

Clinical Reader in Vascular Molecular Pathology
 
 
 
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Contact

 

+44 (0)20 7594 2723joseph.boyle Website

 
 
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Location

 

L536ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Khamis:2016:10.1038/srep21785,
author = {Khamis, RY and Woollard, KJ and Hyde, GD and Boyle, JJ and Bicknell, C and Chang, S-H and Malik, TH and Hara, T and Mauskapf, A and Granger, DW and Johnson, JL and Ntziachristos, V and Matthews, PM and Jaffer, FA and Haskard, DO},
doi = {10.1038/srep21785},
journal = {Scientific Reports},
title = {Near Infrared Fluorescence (NIRF) Molecular Imaging of Oxidized LDL with an Autoantibody in Experimental Atherosclerosis},
url = {http://dx.doi.org/10.1038/srep21785},
volume = {6},
year = {2016}
}
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RIS format (EndNote, RefMan)

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  -
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