Antibody-targeted photodynamic therapy.
PURPOSE: To assess the feasibility of conjugation of verteporfin (Visudyne, Parkedale Pharmaceuticals, Rochester, Minnesota, USA) to antibody against vascular endothelial growth factor. DESIGN: Experimental study. METHODS: Rabbit antimouse vascular endothelial growth factor polyclonal antibody was conjugated to verteporfin. Fluorescence excitation-emission spectra of verteporfin and conjugate were examined. Vascular endothelial growth factor-expressing murine endothelial cells were incubated with saline, verteporfin, or conjugate, followed by laser exposure or no laser exposure. Cell viability at 1 and 24 hours was assessed via trypan blue exclusion. Results were analyzed by two-way analysis of variance with replication and the Bonferroni multiple comparison test. RESULTS: The fluorescence excitation-emission spectrum of the conjugate was similar to that of verteporfin. After laser exposure, cell viability in conjugate-treated cells was reduced to 6% at 1 hour (P <.0001) and to 4% at 24 hours (P <.0001), compared with approximately 40% in nonlaser-exposed, conjugate-treated cells. The cytotoxicity in the conjugate-treated cells was higher than in verteporfin-treated cells exposed to laser, although the difference did not reach statistical significance. CONCLUSIONS: The conjugation of verteporfin to polyclonal antibody is possible without the loss of its photosensitizing properties. Conjugated verteporfin destroys cellular targets at least as effectively as verteporfin alone.
Mayo, GL; Melendez, RF; Kumar, N; McKinnon, SJ; Glickman, RD
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