benzoporphyrin-d and Iris-Neoplasms

Benzoporphyrin derivative (BPD), a sensitizer currently in clinical trials, was evaluated for the treatment of experimental Greene melanoma implanted in the rabbit iris. To improve tumor targeting, BPD was complexed with low-density lipoprotein (LDL) representing an endogenous carrier system for BPD as previously described. Twelve tumors were irradiated at a sensitizer dose of 2 mg kg-1 body weight using a dye laser at 692 nm. Tumor responses were documented by photography, angiography and light and electron microscopy. All tumors treated with 80 J cm-2 regressed irreversibly. The principal mechanism of tumor necrosis was thrombosis following disruption of endothelial membranes. Ultrastructure data suggested tumor cell damage, although evidence for this being the result of direct PDT-mediated tumor cell death was less clear. These data suggest that BPD-LDL may be used to improve the selectivity of photodynamic tumor therapy possibly by the increased uptake of lipoprotein-delivered sensitizer to neovascular endothelial cells.

Topics: Animals; Disease Models, Animal; Drug Carriers; Iris Neoplasms; Lipoproteins, LDL; Melanoma, Experimental; Microscopy, Electron; Photochemotherapy; Porphyrins; Rabbits; Radiation-Sensitizing Agents

Photodynamic therapy (PDT) with its potential for precise localization and absence of severe side effects such as radiation retinopathy may be particularly appropriate for the treatment of intraocular tumors. Benzoporphyrin (BPD), a potent photosensitizer currently in clinical trial, absorbs light at 692 nm, thus allowing sufficient tissue penetration due to minor light absorption in melanin and hemoglobin. The efficiency and selectivity of BPD are significantly pronounced through preassociation with low-density lipoprotein (LDL), since proliferating cells exhibit an increased metabolism of lipoproteins. As an experimental model Greene's melanomas were implanted either into the iris or choroid of albino rabbits. Irradiation at a radiation energy of 80 for iris and 100 J/cm2 for choroidal tumors 3 h after the i.v. injection of BPD-LDL (2 mg/kg) was administered via a laser arrangement with argon-pumped dye-laser, using the slit-lamp. Angiographies and LM/EM histologies were done immediately, and 1, 3, and 14-21 days post-exposure. All 16 treated tumors demonstrated complete regression with a remaining avascular, fibrotic scar. Immediate vascular occlusion within the tumor was seen angiographically, suggesting a direct vascular mechanism. Histologically, two primary mechanisms could be detected: destruction of neovascular endothelial cells and intracellular tumor cell damage. These results indicate that PDT using BPD-LDL complexes may provide an efficient and selective modality for the management of intraocular neoplasms. The availability of new and potent photosensitizers may also lead to broader clinical applications.

Topics: Animals; Choroid; Choroid Neoplasms; Hematoporphyrin Photoradiation; Iris; Iris Neoplasms; Lipoproteins, LDL; Melanoma, Experimental; Porphyrins; Rabbits; Radiation-Sensitizing Agents