Résumé

Meta(tetrahydroxyphenyl)chlorin (m-THPC) is a new photosensitizer currently undergoing clin. trials at Lausanne's CHUV hospital for photodynamic therapy (PDT) of early cancer in the upper aerodigestive tract. The illumination of m-THPC with light at 650 nm in aq. soln. contg. 10% fetal calf serum (FCS) causes two simultaneously occurring processes: its photodegrdn. and the formation of a more stable photoproduct absorbing at 320 nm. The photodegrdn. quantum yield (FPb) of m-THPC is found to be of the order of 1.5*10-5 in 10% FCS. A strong dependence on oxygen concn. of the photodegrdn. and the formation of photoproducts has been obsd. Indeed, the m-THPC presents rather low FPb under N2-satd. conditions: 6.9*10-6. In aerobic conditions, the photodegrdn. as well as the formation of photoproducts, have been competitively inhibited by known singlet oxygen (1O2) quenchers. The addn. of superoxide dismutase (SOD), catalase or desferal, known quenching agents of type I mechanisms, has little or no effect on the rate of photobleaching and photoproduct formation of m-THPC. m-THPC generates 1O2 with a quantum yield of 0.3 in ethanol soln. as detd. by photo-oxidn. expts. using 1,3-diphenylisobenzofuran (DPBF) as substrate. The rate and quantum yield of DPBF photo-oxidn. are found to increase with increasing substrate concn. and decrease in phosphate buffer soln. (FD=0.01), due to the partially hydrophilic character of m-THPC. In addn., the reaction of 1O2 with TEMP (2,2,6,6-tetramethyl-4-piperidone) in combination with ESR (EPR) detection has been used to det. the formation of 1O2 by m-THPC in ethanol soln.

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