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Colin A. Bretz, Ashwath Jayagopal; Nanotechnology Guided Molecular Imaging of Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3006.
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Strategies for the early detection of choroidal neovascularization are needed to facilitate timely therapeutic intervention and to monitor disease progression and treatment response. Ligand-coated nanoparticles were developed for site-specific imaging of neovascular lesions in animal models of laser-induced choroidal neovascularization.
Infrared dyes and fluorescent semiconducting nanocrystals (quantum dots) were conjugated to peptides or antibodies directed against vascular cell adhesion molecule 1 (VCAM-1), an early marker of choroidal neovascularization, using covalent conjugation techniques. Negative controls were synthesized incorporating scrambled peptide or nonspecific antibody conjugated imaging agents. Conjugates were injected in mouse models of laser-induced choroidal neovascularization at timepoints up to 31 days post laser injury, and age matched controls. Ocular tissue was imaged ex vivo and in vivo throughout the time course of choroidal neovascularization for evaluation of specificity and sensitivity.
VCAM-1 targeted imaging agents were capable of early detection of choroidal neovascularization via binding to VCAM-1. VCAM-1 signal remained elevated throughout the time course of pathology, up to 1 month post laser injury. Signal to background ratios of VCAM-1 specific imaging agents ranged from 10-25:1 depending on the disease timepoint, and fluorescence emission was focal to CNV lesions. Negligible binding of imaging agents was observed in control animals.
Successful detection of early choroidal neovascularization was possible in the mouse model of laser induced choroidal neovascularization. Molecular imaging of the eye is a promising strategy for facilitating early detection of disease, which may improve clinical management of neovascular AMD.
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