PHOTODYNAMIC THERAPY WITH M-TETRAHYDROXYPHENYLCHLORIN IN-VIVO - OPTIMIZATION OF THE THERAPEUTIC INDEX

The therapeutic index of meta-tetrahydroxyphenylchlorin-mediated photo dynamic therapy (mTHPC-PDT) was assessed in BALB/c nude mice bearing h uman malignant mesothelioma xenografts. Equal doses of 650 nm laser li ght were delivered to the tumour and to an equal-sized area of the hin d leg (control site) after i.p. administration of mTHPC. Twenty-one gr oups of 6 animals each were treated under various drug-light condition s and at drug-light intervals ranging from 4 hr to 6 days. After light delivery the extent of tumour necrosis and the depth of alterations i n normal tissue were assessed by light microscopy of standardized hist ological sections. A therapeutic index (TI) of mTHPC-PDT was defined a s the cross-sectional area of tumour necrosis per depth of visible tis sue injury at the control site. This TI was strongly related to the co nditions of treatment. In particular, it was increased by prolonging t he drug-light interval up to 5 days and by increasing the dose of ligh t for any dose of drug. The most profound increase of TI was obtained by increasing the intensity of light administered at the chosen interv al while reducing the dose of drug. Our findings suggest that threshol d conditions operate in PDT and have important implications for clinic al application of the treatment. (C) 1993 Wiley-Liss, Inc.