chloroaluminum-tetrasulfophthalocyanine and Fibrosarcoma

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

Very little is known about the applicability of the metabolic and biochemical events observed in cell culture systems to in vivo tumor shrinkage following photodynamic therapy (PDT). The purpose of this study was to assess whether PDT induces apoptosis during tumor ablation in vivo. We treated radiation-induced fibrosarcoma (RIF-1) tumors grown in C3H/HeN mice with PDT employing three photosensitizers, Photofrin-II, chloroaluminum phthalocyanine tetrasulfonate, or Pc IV (a promising phthalocyanine developed in this laboratory). Each photosensitizer was injected intraperitoneally and 24 h later the tumors were irradiated with an appropriate wavelength of red light using an argon-pumped dye laser. During the course of tumor shrinkage, the tumors were removed at 1, 2, 4 and 10 h post-PDT for DNA fragmentation, histopathologic, and electron microscopic studies. Markers of apoptosis, viz. the ladder of nucleosome-size DNA fragments, increased apoptotic bodies, and condensation of chromatin material around the periphery of the nucleus, were evident in tumor tissue even 1 h post-PDT; the extent of these changes increased during the later stages of tumor ablation. No changes were observed in tumors given photosensitizer alone or irradiation alone. Our data suggest that the damage produced by in vivo PDT may activate endonucleolysis and chromatin condensation, and that apoptosis is an early event in tumor shrinkage following PDT.

Topics: Animals; Apoptosis; Dihematoporphyrin Ether; DNA Damage; DNA, Neoplasm; Fibrosarcoma; Indoles; Mice; Mice, Inbred C3H; Organometallic Compounds; Organosilicon Compounds; Radiation-Sensitizing Agents; Silanes; Skin Neoplasms; Ultraviolet Therapy

The potency of chloroaluminum sulfonated phthalocyanine (ClAlSPc) as a photosensitizing agent for photodynamic therapy of cancer was evaluated in vivo by its ability to be taken up and retained by murine tumors of diverse histological origin. Antitumor effects following laser irradiation were evaluated by measurement of the tumor weights of dissected-out tumor masses. Three tumors (Colo 26, a colorectal carcinoma; M5076, a reticulum cell sarcoma; and UV-2237, a fibrosarcoma) growing s.c. in the flank region retained substantially greater quantities of ClAlSPc than did adjacent skin and muscle achieving peak values 24-48 h after the i.v. administration of ClAlSPc (10 mg/kg). The relative magnitude of ClAlSPc retention by these tumors was Colo 26 greater than M5076 greater than UV-2237. However, normal liver and spleen were organs which retained the greatest amounts of ClAlSPc even compared to the s.c. grown tumors and other normal tissues examined. Flow cytometric analysis of tumor cell suspensions obtained from collagenase-digested tumors showed that individual neoplastic cells were capable of taking up and retaining ClAlSPc. Photodynamic therapy, undertaken by i.v. administration of dye (5 mg/kg) followed 24 h later by local laser light irradiation (675 nm, 100 J), brought about significant (Colo 26, M5076, and 3LL tumors) and obvious but nonsignificant (UV-2237 tumor) reductions in tumor weights, as assessed 5 days later. Thus, selective tumor retention of ClAlSPc coupled with a significant response to red light produced dramatic alterations in cancer growth.

Topics: Aluminum; Animals; Cell Line; Colonic Neoplasms; Fibrosarcoma; Indoles; Kinetics; Laser Therapy; Lymphoma, Large B-Cell, Diffuse; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Organometallic Compounds; Photochemotherapy; Radiation-Sensitizing Agents; Tissue Distribution