Imperial College London

Professor Paul M. Matthews

Faculty of MedicineDepartment of Brain Sciences

Edmond and Lily Safra Chair. Head of Department
 
 
 
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Contact

 

+44 (0)20 7594 2855p.matthews

 
 
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Assistant

 

Ms Siobhan Dillon +44 (0)20 7594 2855

 
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Location

 

E502Burlington DanesHammersmith 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}
}

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 -