In Vivo Imaging of Fluorescent Probes Linked to Antibodies Against Human and Rat Vascular Endothelial Growth Factor.

作者: Johanna H. Meyer , Alexander Cunea , Kai Licha , Pia Welker , Dagmar Sonntag-Bensch

DOI: 10.1167/IOVS.15-18118

关键词:

摘要: Purpose Anti-VEGF therapy has improved functional outcome for many patients with neovascular AMD. A particular challenge in routine clinical application is to find the best treatment regimen as a high degree of interindividual variability disease activity been noted. The aim study was investigate fluorescent probes linked antibodies against VEGF vivo imaging an animal model. Methods Bevacizumab, B20-4.1.1 and AF564 were covalently attached novel dye 6S-indocyanine green (ICG) maleimide. Binding proliferation properties assessed. In rat model laser-induced choroidal neovascularization, retinal uptake topographic localization antibody-conjugates analyzed. Distribution accumulation determined by immunohistochemistry flow cytometry analysis. Results Antibody-conjugates retained target binding affinity showed no toxicity. strong fluorescence immediately following intravenous or intravitreal injection. While within laser lesions visualized all three antibody conjugates, signal strength duration varied. addition, distinct spots also recognized. Patterning in-depth analyses including histology data strongly suggest that represent labeled microglial cells and/or macrophages. Conclusions Pharmacokinetics fluorescent-labeled bevacizumab, can be investigated vivo. this model, interpretation long-term observations difficult because possible rat-specific immune response challenges image localized soluble VEGF. Further investigations primate use appropriate directed VEGF-receptor may alternative approaches.

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