Key result
LO1-750 specifically localized to oxidized LDL in atherosclerotic plaques, demonstrating significantly higher uptake in Ldlr-/- mice compared to wild-type controls (25.3 vs 1.3 pmol, p<0.005).
Why the study?
Does LO1-750 specifically localize to and quantify oxidized LDL in experimental atherosclerosis models?
Does LO1-750 specifically localize to and quantify oxidized LDL in experimental atherosclerosis models?
Absolute Event Rate: 25.3% vs 1.3%
p-value: p=<0.005
LO1-750, a NIRF-labeled autoantibody targeting oxidized LDL, successfully localizes to and quantifies atherosclerotic plaque burden in experimental models, demonstrating potential for non-invasive molecular imaging of vulnerable plaques.
Does not yet support clinical use of LO1-750; leaves open its potential as an atherosclerosis imaging agent.
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.
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Khamis et al. (2016) studied Atherosclerosis. LO1-750 vs. IgG3-750 (isotype control) or Wild-type mice was evaluated on NIRF signal quantification of LO1-750 uptake in the aortic arch and branches (p=<0.005). LO1-750 specifically localized to oxidized LDL in atherosclerotic plaques, demonstrating significantly higher uptake in Ldlr-/- mice compared to wild-type controls (25.3 vs 1.3 pmol, p<0.005).
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