chloroaluminum-tetrasulfophthalocyanine and Carcinoma--Squamous-Cell

Topics: Animals; Carcinoma, Squamous Cell; Cat Diseases; Cats; Dog Diseases; Dogs; Fibrosarcoma; Hemangiopericytoma; Indoles; Neoplasms; Organometallic Compounds; Photosensitizing Agents; Tissue Distribution; Tumor Cells, Cultured

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinoma; Carcinoma, Squamous Cell; Cheek; Cricetinae; Fluorometry; Indoles; Lasers; Male; Mesocricetus; Mouth Neoplasms; Neoplasm Transplantation; Organometallic Compounds; Radiation-Sensitizing Agents; Tissue Distribution

Photodynamic therapy (PDT) of cancer is an experimental tumor therapy which is based on the combined use of a systematically administered photosensitizer to a tumor-bearing host and local illumination of the lesion by a high-intensity visible light source, typically a tunable argon dye laser. Human squamous cell carcinoma (HSCC) is the most frequently encountered malignancy of the head and neck. In this study, responses of HSCC cells to PDT were examined in in vitro and in vivo systems. In in vitro studies, the HSCC cells showed a positive photodynamic response with Photofrin-II (Pf-II), chloroaluminum phthalocyanine tetrasulfonate (AlPcTS), and a newly synthesized silicon phthalocyanine (SiPc IV). Single cell suspension of HSCC injected subcutaneously on the back of athymic nude mice resulted in a well-circumscribed tumor mass. The animals required a low tumor dose for the successful establishment of a tumor. The tumor was minimally immunogenic and showed neither macroscopic signs of early metastasis to lung, kidney, liver, or spleen nor evidence of surrounding erythema, fluctuation, or tenderness until the late stages of necrosis. Intraperitoneal administration of AlPcTS or SiPc IV to tumor-bearing mice resulted in rapid uptake of the photosensitizers in liver, skin, and tumor tissue. Twenty-four hours following the intraperitoneal administration of AlPcTS or SiPc IV to tumor-bearing animals, the tumor to normal skin ratio of the photosensitizer was 1.6 or 1.5, respectively. Administration of Pf-II (5 mg/kg) to tumor-bearing animals followed 24 hours later by irradiation of the tumor (135 J/cm2, 630 nm light from an argon pumped-dye laser) resulted in greater than 80% ablation in tumor volume 24 hours post-PDT. These characteristics make this tumor model system suitable for PDT studies of human tumor cells in vitro as well as in vivo.

Topics: Aluminum; Animals; Carcinoma, Squamous Cell; Cell Death; Cell Division; Dihematoporphyrin Ether; Humans; Indoles; Liver; Mice; Mice, Nude; Neoplasm Transplantation; Organometallic Compounds; Organosilicon Compounds; Photochemotherapy; Photosensitizing Agents; Radiation-Sensitizing Agents; Silanes; Skin; Skin Neoplasms; Thymidine; Transplantation, Heterologous; Tritium; Tumor Cells, Cultured

Aluminum-chloro-tetrasulfonated phthalocyanine (PC) showing an absorption peak at 678 nm was compared to hematoporphyrin derivative (HpD), a photosensitizer commonly used in the photodynamic therapy (PDT) of cancers.. KK-47 cells were exposed to long-wavelength ultraviolet (UVA) or red light (greater than 600 nm, greater than 640 nm and greater than 660 nm) after drug sensitization. With UVA irradiation, a higher photodynamic cell killing effect was observed in the cells treated with HpD than with PC. However, with red light irradiation (both greater than 640 nm and greater than 660 nm) PC resulted in greater cell damage. PC was less toxic to KK-47 cells in the dark. In vivo studies: Using a gold vapor laser (GVL: 627.8 nm, 200 mW/cm2, 200 J/cm2), the photodynamic tumor response was determined in C3H/He mice bearing transplantable squamous cell carcinoma. No significant difference was observed in the tumor volume between the PC and HpD groups, except that the PC group (10.0 mg/kg body weight) showed a significantly higher remission rate (3/6) than the control group (0/10, P less than 0.05). Skin photosensitivity test: Skin photosensitivity was estimated by measuring changes in back skin thickness due to photosensitization. With UVA irradiation, a stronger skin reaction was observed in the HpD group, while with visible light irradiation there was no significant difference between the HpD and PC groups. Based on the superior cell killing effect with red light, reduced toxicity to the cells in the dark and mild skin reaction with UVA, PC may be a more promising photosensitizer for PDT.

Topics: Animals; Carcinoma, Squamous Cell; Cell Survival; Hematoporphyrin Photoradiation; Humans; Indoles; Isoindoles; Lasers; Mice; Mice, Inbred C3H; Organometallic Compounds; Photochemotherapy; Skin; Tumor Cells, Cultured; Urinary Bladder Neoplasms