bacteriochlorophylls and temoporfin

Debate is ongoing about the treatment of organ-confined prostate cancer, particularly in men who have low-risk disease detected by PSA screening. A balance is needed between the harms and benefits of treatment. New techniques are being developed that aim to offer similar treatment effects to current radical therapies, while reducing the associated harmful effects of these treatments. In this Review, we explore the potential of one such technique, photodynamic therapy (PDT), for the treatment of organ-confined prostate cancer. PDT uses a photosensitizing drug that is activated in the prostate by low-power laser light, delivered using optical fibers. The fibers are placed within needles in the prostate, guided by transrectal ultrasound and a perineal template. Following the activation of the photosensitizer by light, and the formation of reactive oxygen species, necrosis occurs at the site of interaction between the photosensitizer, light and oxygen. Clinical studies are underway to investigate the use of PDT for primary and salvage treatment of organ-confined prostate cancer. We review these studies, the potential strategies for enhanced photodynamic effects, and the current limitations of PDT for prostate cancer.

Topics: Bacteriochlorophylls; Forecasting; Humans; Male; Mesoporphyrins; Photochemotherapy; Photosensitizing Agents; Prostatic Neoplasms

Photodynamic therapy induces the production of reactive oxygen species (ROS) within tissues exposed to laser light after administration of a sensitizer. In the context of continuing clinical and commercial development of chemicals with sensitizing properties, a minimally invasive assay is needed to determine the tissue kinetics of fluorescent or non-fluorescent photoreactive drugs. The level of ROS was determined ex vivo from 1 mm3 biopsy samples using 2'-7' dichlorofluorescin diacetate (DCFH-DA), a fluorescent probe which was converted into highly fluorescent dichlorofluorescein (DCF) in the presence of ROS. This assay was tested on meta(tetrahydroxyphenyl)chlorin (m-THPC, FOSCAN), a powerful and fluorescent sensitizer, and bacteriochlorophyll derivative WST09 (TOOKAD), a near-infrared absorbing sensitizer that is only slightly fluorescent. In conjunction with the ROS assay, the tissue accumulation of m-THPC was determined on biopsy samples using an optic fibre spectrofluorometer (OFS). DCF fluorescence was proportional to the level of oxidation induced by horseradish peroxidase used as a control and to the concentration (range: 0-5 microg x ml(-1)) of both selected photosensitizers irradiated in a tube together with DCFH. Regardless of the organ studied, an excellent correlation was found between fluorescence measurement by OFS and ROS determination for m-THPC. m-THPC (2 mg x kg(-1) iv) accumulation in tumour tissues was best after 48 h, and the best signal was obtained in liver. With non-fluorescent WST09 (2 mg x kg(-1)), ROS determination showed the best tumour uptake 48 h after injection, with a tumour/muscle ratio of 5.4. The ROS assay appears to be feasible for determining sensitizer concentration in regular grip biopsy tissue samples.

Topics: Animals; Bacteriochlorophylls; Dose-Response Relationship, Drug; Fluoresceins; HT29 Cells; Humans; Male; Mesoporphyrins; Mice; Photosensitizing Agents; Reactive Oxygen Species; Spectrometry, Fluorescence