aluminum-phthalocyanine-disulfonate and aluminum-phthalocyanine

The efficacy of photodynamic therapy (PDT) mediated by aluminium phthalocyanine (AlPc) and its mono- and disulphonated derivatives (AlPcS1 and AlPcS2, respectively) on murine EMT-6 tumour were compared in vivo. AlPc (0.25 mumol/kg) PDT resulted in no tumour recurrence in all treated mice. In contrast, PDT with AlPcS1 (2 mumol/kg) and AlPcS2 (1 mumol/kg) only produced tumour cure in 75% and 86% of mice, respectively. Immediately after AlPc-PDT, tumour cells were found to be viable as determined by in vitro clonogenicity, but progressive cell death occurred thereafter. In contrast, AlPcS1 and AlPcS2 PDT produced substantial cell death (approximately 35% and 70%, respectively, of entire tumour) immediately after phototherapy, and yet further loss of tumour cell viability continued after PDT. In all cases, few vascular effects were observed at 0 h post-PDT, as indicated by the retention of 99mTc-MIBI in the tumour. However, the reduction of blood flow in tumours progressed with time, such that blood flow in tumours fell to approximately 25% of the control level by 24 h after both AlPc and AlPcS1 PDT. With AlPcS2, there was only an approximate 50% fall in tumour blood flow by 24 h. These results demonstrate a greater PDT efficiency with AlPc on tumour destruction, which is an indirect mechanism involving damage of tumour vasculature, whereas AlPcS2 has a greater effect on direct tumour cytotoxicity and AlPcS1 exerts both direct and indirect modes of action against tumours.

Topics: Animals; Cell Survival; Indoles; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Organometallic Compounds; Photochemotherapy; Radiation-Sensitizing Agents; Sarcoma, Experimental; Tumor Cells, Cultured

By means of laser scanning fluorescence microscopy the intratumoral localization patterns of several photosensitizers in LOX tumors in nude mice were studied. Lipophilic dyes such as TPPS1 (tetraphenylporphine monosulfonate), TPPS2a (tetraphenylporphine disulfonates with the sulfonate groups on adjacent rings), AlPCS1 (aluminium phthalocyanine monosulfonate) and AlPCS2 (aluminium phthalocyanine disulfonates) localized mainly in tumor cells. The fluorescence intensity of these dyes increased from 4 h to 48 h postinjection and the fluorescence was still observable 120 h postinjection. The more hydrophilic dyes such as TPPS3 (tetraphenylporphine trisulfonates), TPPS4 (tetraphenylporphine tetrasulfonates), and AlPCS4 (aluminium phthalocyanine tetrasulfonates) localized mainly extracellularly in the tumorous stroma. The fluorescence intensity of these dyes decreased from 4 h to 48 h postinjection. 120 h postinjection no significant fluorescence of these dyes could be seen in the tumors. P-II (Photofrin II), 3-THPP [tetra(3-hydroxyphenyl)porphine], TPPS2o (tetraphenylporphine disulfonates with the sulfonate groups on opposite rings) and AlPCS3 (aluminum phthalocyanine trisulfonates) had a combined localization pattern, i.e. a strongly cytoplasmic membrane-localizing pattern and a weakly intracellular distribution pattern, although some fluorescence could be seen in the tumorous stroma. The data are discussed in relation to what is known about the in vivo photosensitizing efficiency of some of the dyes.

Topics: Animals; Cell Line; Dihematoporphyrin Ether; Female; Fluorescent Dyes; Hematoporphyrins; Humans; Indoles; Lasers; Melanoma; Mice; Mice, Inbred BALB C; Mice, Nude; Microscopy, Phase-Contrast; Organometallic Compounds; Photochemotherapy; Porphyrins; Radiation-Sensitizing Agents