Zinc Phthalocyanine Tetrasulfonate (ZnPcS4): A New Photosensitizer for Photodynamic Therapy in Choroidal Neovascularization

Abstract

The aim of this sutdy was to demonstrate the selective localization of a new photosensitizer, zinc phthalocyanine tetrasulfonate (ZnPcS(4)), in rat eyes and investigate the ability of ZnPcS(4) to produce a photochemical closure of experimental choroidal neovascularization (CNV) upon irradiation with a 670-nm laser light. To determine the biodistribution of ZnPcS(4) and the optimal timing of laser irradiation after photosensitizer administration, fluorescence microscopy with ZnPcS(4) was performed. CNV was created in the fundi of Brown-Norway rats using the argon laser model and documented by fluorescein angiography (FFA) and optical coherence tomography (OCT). Photodynamic therapy (PDT) was performed at the dose of 2.0 mg/m(2) and laser fluences of 600 mW/cm(2) on the CNV and on normal retina and choroid. Treatment outcomes were assessed by FFA and OCT and confirmed by light and electron microscopy. Fluorescence microscopy demonstrated intense ZnPcS(4) fluorescence from the CNV, choriocapillaris, and retinal pigment epithelial cells. Peak ZnPcS(4) intensities in the choriocapillaris and CNV were detected at 10-20 min after an intravenous injection. FFA and OCT indicated that irradiation with 670 nm of laser light 20 min after a ZnPcS(4) injection produced a complete closure of CNV with minimal damage to the overlying retina. Histologic studies, using light and electron microscopy, demonstrated CNV endothelial cell necrosis with minimal damage to the surrounding tissues. ZnPcS(4) selectively localizes to the choriocapillaris and CNV in rats, resulting in the occlusion of laser-induced CNV with minimal damage to the retina tissues. ZnPcS(4) -PDT is a potential new strategy for the treatment of macular degeneration and other human diseases manifesting as CNV.