chloroaluminum-tetrasulfophthalocyanine and Colonic-Neoplasms

The sonodynamically induced antitumour effect of chloroaluminum phthalocyanine tetrasulfonate (AlPcTS) was evaluated on subcutaneously implanted colon 26 carcinoma. A time of 24 h after the administration of AlPcTS was chosen for the ultrasonic exposure, based on the analysis of the AlPcTS concentrations in the tumour, plasma, skin and muscle. The pharmacokinetic analysis showed much faster clearance of AlPcTS than photofrin II from the body, which can be an advantage in view of their potential adverse effects. At an AlPcTS dose not less than 2.5 mg kg(-1) and at a free-field ultrasonic intensity not less than 3 W cm(-2), the synergistic effect between AlPcTS administration and ultrasonic exposure on the tumour growth inhibition was significant. The ultrasonic intensity showed a relatively sharp threshold for the synergistic antitumour effect, which is typical for an ultrasonic effect mediated by acoustic cavitation. These results suggest that AlPcTS is a potential sonosensitizer for sonodynamic treatment of solid tumours.

Topics: Animals; Area Under Curve; Cell Line, Tumor; Colonic Neoplasms; Dihematoporphyrin Ether; Indoles; Male; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Organometallic Compounds; Photosensitizing Agents; Tissue Distribution; Ultrasonic Therapy

Phototoxicity of intra-tumoral injected methylene blue (MB+) was studied in 48 experimental colonic tumours in comparison with photosan-3, Zn-phthalocyanine and tetrasulphanated ClAl-phthalocyanine.. In mice. xenotransplanted subcutaneous tumours about 1 cm in diameter were treated photodynamically twice, with different sensitisers. The irradiation was performed at the sensitiser-specific wavelength, and a density of 100 mW/cm2 and a dose of 100 J/cm2.. Light alone without sensitiser did not induce any effect in mice tumours. Surprisingly, Al-phthalocyanine could only be used for intratumoral injections because of toxic effects after intravenous applications in nude mice. Using MB+ (1%), 75% of the tumours were destroyed by a single photodynamic treatment (PDT). In addition, toxicity of MB+ was most intense when compared with Zn-phthalocyanine and photosan-3. However, after the second PDT, there was no statistically significant difference among these sensitisers. Dark toxicity of MB+ (1%) could be well demonstrated by sufficient sensitiser incorporation without irradiation, which led to a stationary tumour volume up to 3 weeks after injection.. Intra-tumoral MB+ PDT is a potential treatment for inducing necrosis in vivo. With regard to tumour tissue, the selectivity of MB+ is high and depends on a precise local injection of the dye.

Topics: Animals; Colonic Neoplasms; Female; Hematoporphyrins; Indoles; Injections, Intralesional; Isoindoles; Methylene Blue; Mice; Mice, Nude; Neoplasm Transplantation; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Zinc Compounds

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

Topics: Animals; Colonic Neoplasms; Indoles; Male; Mice; Mice, Inbred BALB C; Organometallic Compounds; Photochemotherapy; Radiation-Sensitizing Agents