Selective and Safe PDT in the Monkey Using WST11, a Water Soluble Bacteriochlorophyll Derivate

Abstract

Purpose:: We have previously demonstrated that WST11 is efficient to occlude selectively CNV in rats without causing collateral damages. The aim of this study was to define the optimal parameters of WST11 PDT in the monkey eye prior to clinical evaluation.

Methods:: Choroidal CNV was induced in 12 eyes of cynomolgus macaques using argon laser (50µm, 575 mW, 0.1 seconds). Fourteen days after photocoagulation, fluorescein (FA) angiograms ascertained the presence of CNV in about 30% of the laser photocoagulation sites. Two doses of WST11 (2.5 and 5mg/Kg) were tested. Illumination was performed with a 753 nm laser using intensities of 25, 50 or 100J/cm². Distance to light illumination (DLI) of 1, 5 and 10 min were also evaluated. FA were performed immediately after treatment 2, 8, 15, 21 and 28 days after WST11 PDT. With the defined selective occlusive parameters, two monkeys were sacrificed at day 3 post-treatment. To assess the effects of WST11 PDT, semi-thin and ultrathin histology sections of the lesion site were performed at each treatment time point. Flat mounted retina and choroids after FITC dextran perfusion were evaluated at day 3. Pharmacokinetics of WST11 were recorded in the serum.

Results:: Using 25J/cm² with any of the WST11 doses or DLI, no vessel occlusion was observed. On semi-thin sections, the RPE cells and photoreceptors of treated areas around the lesion did not show any structural damage. Treatment with 100J/cm² and 5mg/Kg WST11, DLI 1min or 5 min, non-selective occlusion of both choroidal and retinal vessels was observed with subsequent ischemic damages to the retina. Using WST11 2.5mg/Kg, and 50 J/cm², DLI 1 or 5 min, selective and stable occlusion of the CNV was observed on FA and confirmed by both flat-mounted retina and choroids at day 3 and semi or ultrathin histology at day 3, 8, and 21. No sub retinal or intraretinal fluid occurred at any time points after PDT. No significant collateral damages resulted from WST11 PDT using selective parameters.

Conclusions:: Using well defined parameters, WST11 induces an efficient, selective and stable occlusion of CNV around the photocoagulated lesion in the monkey CNV model. The lack of collateral damage to the RPE and retina using WST11 indicates the potential for PDT selective therapeutic effects of this drug.

Keywords: photodynamic therapy • choroid: neovascularization • drug toxicity/drug effects