THE EFFICACY OF AN IRON CHELATOR (CP94) IN INCREASING CELLULAR PROTOPORPHYRIN-IX FOLLOWING INTRAVESICAL 5-AMINOLEVULINIC ACID ADMINISTRATION - AN IN-VIVO STUDY

5-Aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX) is provi ng to be a useful photosensitizer for photodynamic therapy (PDT). Conv ersion of PpIX to haem requires catalysed chelation with iron, and thu s the presence of an iron chelator should, in theory, lead to an incre ase in cellular PpIX accumulation. This paper assesses the in vivo eff ect of a new iron chelator, 1,2-diethyl-3-hydroxypyridin-4-one (CP94), on the kinetics of PpIX in different layers of the bladder wall. Wist ar rats were given 1% or 10% ALA intravesically with or without intrap eritoneal CP94. The biodistribution of ALA-induced PpIX in the bladder was evaluated using fluorescence microscopy. Photodynamic effects on the bladder were compared in rats receiving various drug dosimetries. In CP94-treated rats, 5-7 h after administration of 10% ALA solution, the fluorescence intensity of PpIX in the urothelium was doubled compa red with animals given ALA alone, whereas in the muscle layer PpIX rem ained at a low level similar to that found without the iron chelator. At an ALA concentration of 1%, although the PpIX concentration was not increased with CP94, the urothelial selectivity of PDT compared with the muscle layer was enhanced. In conclusion, by using CP94, a further reduction in skin photosensitization may be possible as similar photo dynamic effects can be achieved with a lower dose of ALA, The addition of CP94 seems to be an effective and convenient way to potentiate ALA -induced PpIX tissue selectivity between the urothelium and the underl ying layers of the bladder wall. (C) 1997 Elsevier Science S.A.