PDT with TOOKAD^® studied in the chorioallantoic membrane of fertilized eggs

Summary 

Background:

The potential application of TOOKAD^®–PDT for the treatment of blood vessels was investigated. TOOKAD^® (WST09), a novel palladium-bacteriopheophorbide absorbs light in the near IR with a high quantum yield of intersystem crossing. Our study assessed the efficacy of this drug in inducing vascular damage with a view to its possible use in the treatment of age-related macular degeneration.

Methods:

Vascular damage of TOOKAD^®-PDT was studied in neovessels of the chorioallantoic membrane of fertilized eggs. Pharmacokinetic investigations were done by video microscopy and laser scanning microscopy. To induce damage vessels were irradiated with 763nm light from a diode laser.

Results:

TOOKAD^® was accumulated in the vessels in the first minutes following injection. TOOKAD^® fluorescence was seen predominantly in the lumen and not in the vascular endothelial layer. Although fluorescence was very weak it could be attributed to TOOKAD^® from the fluorescence spectrum in the circulation. Damage assessment was done 24h after application of 763nm light. No significant difference in the degree of damage was observed with different short drug-light intervals (1–10min), but damage increased with the light energy dose. Closure of smaller vessels and vanished capillaries could be achieved by irradiation with 5J/cm² and a TOOKAD^® dose of 33μg/embryo, corresponding to a phototoxic efficacy of 0.0062.

Conclusions:

From the results discussed in this work, TOOKAD^® could be a potential drug for the PDT of age-related macular degeneration in which the growth of new vessels in the choroids can lead to loss of vision.

Keywords: Photodynamic therapy, Vascular effects, CAM model, WST09, AMD