zn(ii)-phthalocyanine and temoporfin

5,10,15,20-Tetra(m-hydroxyphenyl)chlorin (m-THPC, Foscan) is an extremely powerful photosensitizer showing up to 200 times the photodynamic activity of Photofrin in patients, in terms of drug/light dose. The influence of treatment conditions on the photodynamic efficacy of m-THPC has been compared to polyhematoporphyrin (PHP), a Photofrin equivalent, and a cationic pyridinium zinc (II) phthalocyanine (PPC), using the RIF-1 cell line. As predicted, the presence of serum during sensitizer incubation reduced the photodynamic efficacy of all three sensitizers. However, the presence of serum during the illumination period only had an inhibitory effect with PHP and PPC but not m-THPC. Quantification of the intracellular levels of sensitizer revealed that this was due to the efflux of PPC and PHP but not m-THPC into the medium, suggesting that m-THPC is tightly sequestered on entering the cell. This may partially explain the high efficacy of m-THPC in clinical photodynamic therapy and also highlights the importance not only of incubation conditions but also illumination conditions when in vitro comparisons are performed.

Topics: Animals; Cell Line; Culture Media; Hematoporphyrins; Humans; Indoles; Isoindoles; Mesoporphyrins; Mice; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Zinc Compounds

The photodynamic therapy is a technique by which the tumor cells are selectively sensitized to destruction by light of an appropriate wavelength. The aim of this work is to analyze the biological effectiveness of photochemical reactions induced by laser light in tumor cells exposed to photosensitizers.. The toxicity of the 2 photosensitizers zinc phthalocyanine (ZnPC) and meso-tetrahydroxyphenylchlorine (m-THPC) as well as the biological effect of the combination of sensitizers with laser light were tested in vitro by means of a colony forming assay. In addition, the influence on the photodynamic reaction of a previous exposure of the tumor cells to ionizing radiation has been tested.. For both sensitizers doses of 5 micrograms per milliliter of culture medium showed low toxicity, i.e. the survival of the treated cells exceeded 90%. For laser treatments the dose permitting 90% survival was determined to be around 10 J/cm2. With these doses, the combined application of photosensitizers and laser light proved to be very effective and resulted in a nearly complete reduction of survival. As expected, irradiation of the cells with doses of 1 and 2 Gy of X-rays reduced the survival to 66 and 47%, respectively, compared to untreated controls. Cells surviving such treatment showed no changes either in the response to treatments with photosensitizers or to combined applications of photosensitizers and laser light.. The effects of photodynamic treatment by ionizing radiation seem to be additive and independent of each other. So, our preliminary results are quite encouraging and point out the need of further detailed studies in view of the intended clinical application of this new kind of a local treatment.

Topics: Breast Neoplasms; Carcinoma; Combined Modality Therapy; Drug Evaluation, Preclinical; Female; Humans; Indoles; Isoindoles; Laser Therapy; Liposomes; Mesoporphyrins; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Tumor Cells, Cultured; Zinc Compounds

New photosensitizing drugs are becoming available which should improve on some of the disadvantages of haematoporphyrin derivates for photodynamic therapy (PDT). The main features are shorter duration of systemic photosensitisation, activation by longer and more penetrating light and better tumour to normal tissue drug uptake ratios. These drugs together with better understanding of in vivo light dosimetry promise to improve both results and clinical acceptability for PDT in future studies.

Topics: Aminolevulinic Acid; Forecasting; Humans; Indoles; Isoindoles; Mesoporphyrins; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Porphyrins; Zinc Compounds