chloroaluminum-tetrasulfophthalocyanine and Disease-Models--Animal

Chloro-aluminum sulfonated phthalocyanine (CASPc) is a photo-chemically active dye employed in photodynamic therapy (PDT). CASPc is a potent generator of singlet oxygen when irradiated with 675 nm light and is also capable of fluorescence, allowing visualization of the dye in tissues. We devised an angiography system using CASPc fluorescence to determine its localization in experimental choroidal neovascularization in monkeys and then investigated the ability of CASPc to produce photochemical closure of neovascularization upon irradiation with 675nm laser light. Fluorescent imaging indicated that CASPc localized angiographically in areas of neovascularization for at least 24 hours. Irradiation with 675 nm laser light 5-30 minutes after CASPc injection produced complete closure of choroidal neovascularization with minimal damage to overlying retina. We conclude that CASPc localizes in neovascular choroidal vessels and that CASPc photodynamic therapy can produce closure of these choroidal vessels.

Topics: Aluminum; Animals; Choroid; Disease Models, Animal; Fluorescein Angiography; Fundus Oculi; Indoles; Laser Therapy; Macaca fascicularis; Neovascularization, Pathologic; Organometallic Compounds; Photochemotherapy; Radiation-Sensitizing Agents

The aim of this study was to evaluate the possible influence of phthalocyanine dose and of time interval between phthalocyanine injection and irradiation commencement on the rate of experimental corneal neovascularization photodynamic thrombosis in albino rabbits. New corneal vessels were irradiated with a diode laser (670 nm, 2 mW) after the intravenous injection of chloroaluminum sulfonated phthalocyanine. Different animals were irradiated either 5 min after the injection of different phthalocyanine doses (3, 6, 8, 12, or 14 mg/kg), or at different times (5 min, 24 h, or 58 h) after a standard phthalocyanine dose (3 mg/kg) injection. Irradiation time necessary for vascular occlusion was recorded. Decrease of phthalocyanine dose as well as delay of irradiation onset resulted in a statistically significant increase of irradiation time. Electron and light histological examination revealed platelet thrombi inside irradiated corneal new vessels. Damage in the vascular endothelial cell membrane and in intercellular contact structure was noted, leading to disorganization of the endothelial cells layer and death of most endothelial cells. These results indicate that both early commencement of irradiation after phthalocyanine injection and phthalocyanine dose increase accelerate the rate of phthalocyanine mediated corneal neovascularization photodynamic thrombosis. Thrombosis seems to result from photochemically induced vascular endothelial cell damage.

Topics: Aluminum; Animals; Cornea; Corneal Neovascularization; Disease Models, Animal; Indoles; Injections, Intravenous; Laser Therapy; Male; Organometallic Compounds; Photochemotherapy; Rabbits; Radiation-Sensitizing Agents; Thrombosis

Although photodynamic therapy has shown great promise for the treatment of a variety of malignant neoplasms, the role of this new therapeutic modality in the clinical management of intraocular tumors remains incompletely understood. This study examines the effects of photodynamic therapy using chloroaluminum sulfonated phthalocyanine on Greene hamster melanoma transplanted into the subchoroidal space in rabbits. Twenty-four hours after intravenous administration of chloroaluminum sulfonated phthalocyanine (5 mg/kg), tumors were irradiated with 675 nm of light at total light doses of 7 to 60 J/cm2. The results show that tumor growth was arrested at total light doses of 22 to 60 J/cm2. At total light doses of 15 to 21 J/cm2, tumor growth was initially arrested. However, regrowth of these tumors was apparent within 7 days. Total light doses of less than 15 J/cm2 showed no response. Complications of photodynamic therapy, such as intraretinal or subretinal hemorrhages and retinal detachment, were seen only in animals who received total light doses in excess of 43 J/cm2.

Topics: Aluminum; Animals; Choroid Neoplasms; Corneal Edema; Disease Models, Animal; Fluorescein Angiography; Fundus Oculi; Indoles; Light; Male; Melanoma, Experimental; Neoplasm Transplantation; Organometallic Compounds; Photochemotherapy; Rabbits; Radiation-Sensitizing Agents; Retinal Diseases

Photodynamic therapy using chloroaluminum sulfonated phthalocyanine (CASPc) effectively closed experimental iris neovascularization induced in 6 eyes of cynomolgus monkeys by argon laser retinal vein occlusion. Neovascularization was followed by iris photography, fluorescein angiography, and histopathologic examination by light and electron microscopy. Intravenous injection of CASPc followed by irradiation with 675 nm light damaged endothelial cells and pericytes, leading to exposure of the basal lamina and thrombotic occlusion of the blood vessels. Surrounding tissue appeared preserved without evidence of thermal damage. Resorption of occluded vessels by macrophages began 2 to 3 days after photodynamic therapy. Neovascularization reappeared 7 days after photodynamic therapy, probably representing growth of new vessels. Photodynamic therapy with CASPc may be a useful adjunct in the treatment of iris neovascularization. The model is useful in elucidating the ultrastructural changes observed after photodynamic therapy using phthalocyanines.

Topics: Aluminum; Animals; Corneal Diseases; Disease Models, Animal; Endothelium, Corneal; Fluorescein Angiography; Indoles; Injections, Intravenous; Intraocular Pressure; Iris; Laser Therapy; Macaca fascicularis; Neovascularization, Pathologic; Organometallic Compounds; Photochemotherapy; Photography; Recurrence; Retinal Vein Occlusion