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R Renno, Y Terada, MJ Haddadin, FC DeLori, ES Gragoudas, JW Miller; Selective Targeting of Verteporfin to Choroidal Neovascularization Mediated by a Homing Peptide to VEGF-R2 . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3977.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To improve the selectivity and effectiveness of verteporfin/PDT to choroidal neovascularization (CNV) through targeted delivery of verteporfin to CNV combined with anti-angiogenic therapy. Methods: Verteporfin was isolated from its liposomal formulation, linked to a modified polyvinyl alcohol polymer (MW = 10,000), followed by conjugation to "ATWLPPR" using heterobifunctional linking technology. "ATWLPPR" is a peptide reported to specifically bind VEGF-R2 (also known as flk-1 or KDR), completely inhibiting VEGF binding to KDR and preventing VEGF-induced angiogenesis in vivo. Conjugates were separated by reverse phase HPLC. Molecular weight and conjugation rations were determined by mass spectrometry, and emission/excitation spectra were determined for both conjugates and intermediates. PDT activity of the conjugate was tested in vitro using HUVEC and in vivo in normal rat retina. CNV was induced using argon/dye laser in Brown-Norway rat retina. Retinas were immunostained with biotinylated "ATWLPPR". Digital fundus fluorescein angiograms were performed using FITC labeled "ATWLPPR" and FITC labeled control peptide of the same size. Results: The PVA/Verteporfin conjugation ratio was on average 1: 28. The conjugate retained typical emission/excitation spectra and photosensitizing activity, and was as efficient as an equivalent amount of Verteporfin. Immunostaining for "ATWLPPR" was observed in CNV. FITC labeled "ATWLPPR" angiography showed fluorescence within the CNV. Conclusion: elective targeting of Verteporfin to CNV paired with anti-angiogenic treatment may improve PDT efficacy to CNV
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