EFFECT OF DRUG-LIGHT INTERVAL ON PHOTODYNAMIC THERAPY WITH META-TETRAHYDROXYPHENYLCHLORIN IN MALIGNANT MESOTHELIOMA

The influence of the time interval (TI) between drug administration and laser activation on selectivity of meta-tetrahydroxyphenylchlorin(mTHPC)-mediated photodynamic therapy (PDT) for tumour tissue was assessed in BALB/c nude mice bearing human malignant mesothelioma xenografts. Following i.p. administration of 0.3 mg/kg mTHPC, a light dose of 10 J/cm2 and 0.1 W/cm2 was delivered at 650 nm on the tumour and an equal-sized area of the hind leg after 4, 12, 24 and 36 hr and 2, 3, 4, 5 and 6 days to groups of 6 animals (surface irradiance). Then, 72 hr after light delivery, the depth of necrosis was measured in the tumour and in the skin and underlying muscle of the hind leg. Photosensitized necrosis occurred in normal tissue at TI from 4 hr to 3 days and in the tumour at TI from 12 hr to 4 days. The therapeutic ratio of mTHPC-PDT varied significantly with the time interval between drug administration and laser activation and was greatest at an interval of 3 days. mTHPC concentration was measured in 3 control unirradiated animals at all time points in normal tissues and in tumour tissue, and found to be the same in both tissues. Thus the tissue concentration of mTHPC was of limited use as regards the prediction of photosensitizing effects in the tumour model.