<title>Application of 1,2-diethyl-3-hydroxypyridin-4-one to enhance tissue selectivity for photodynamic therapy of the bladder</title>

Abstract

ABSTRACT 5-aminolaevulinic acid(ALA) induced protoporphyrin IX(PpIX) has been proved to be a useful photosensitizer forphotodynamic therapy(PDT). In living cells, the conversion of PpIX to photoinactive haem is catalysed by ferrochelatase inthe presence of tissue iron and inhibition of this final committed step results in increased accumulation of PpIX. The invivo effect of a new iron chelator, 1 ,2-diethyl-3-hydroxypyridin-4-one (CP94) on the buildup of PpIX in different bladder layers was evaluated. In CP94 treated rats, 5-7 hours after intravesical instillation of ALA solution, the fluorescence intensity of PpIX in the urothelium was doubled whilst in the muscle layer it remanied low at a similar level to those seenwithout the iron chelator. With CP94, further reduction of skin photosensitisation is possible as similar photodynamiceffect on the bladder could be achieved at lower ALA concentration. The addition of CP94 seems an effective and convenientway to potentiate ALA induced PpIX tissue selectivity.Keywords: 5-aminolaevulinic acid(ALA), 3-hydroxypyridin-4-ones(HPOs), 1 ,2-diethyl-3-hydroxypyridin-4-one(CP94),bladder instillation, tissue selectivity, Desferrioxamine(DFO), photodynamic therapy(PDT),