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Near Infrared Fluorescence (NIRF) Molecular Imaging of Oxidized LDL with an Autoantibody in Experimental Atherosclerosis.
- Source :
-
Scientific reports [Sci Rep] 2016 Feb 25; Vol. 6, pp. 21785. Date of Electronic Publication: 2016 Feb 25. - Publication Year :
- 2016
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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.
- Subjects :
- Albendazole
Animals
Antigens immunology
Aorta, Thoracic diagnostic imaging
Atherosclerosis diagnostic imaging
Autoantibodies blood
Autoantibodies immunology
Diet, High-Fat
Female
Fluorescent Dyes metabolism
Half-Life
Humans
Immunohistochemistry
Lipoproteins, LDL immunology
Macrophages cytology
Macrophages immunology
Malondialdehyde chemistry
Matrix Metalloproteinases metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Microscopy, Confocal
Microscopy, Fluorescence
Plant Extracts
Rabbits
Receptors, LDL deficiency
Receptors, LDL genetics
X-Ray Microtomography
Atherosclerosis pathology
Autoantibodies chemistry
Fluorescent Dyes chemistry
Lipoproteins, LDL chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 6
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 26911995
- Full Text :
- https://doi.org/10.1038/srep21785