Application of 12-diethyl-3-hydroxypyridin-4-one to enhance tissue selectivity for photodynamic therapy of the bladder

摘要

Abstract: Five-aminolaevulinic acid (ALA) induced protoporphyrinIX (PpIX) has proven to be a useful photosensitizer forphotodynamic therapy (PDT). In living cells, theconversion of PpIX to photoinactive haem is catalyzedby ferrochelatase in the presence of tissue iron andinhibition of this final committed step results inincreased accumulation of PpIX. The in vivo effect of anew iron chelator, 1,2-diethyl-3-hydroxypyridin-4-one(CP94), on the buildup of PpIX in different bladderlayers was evaluated. In CP94 treated rats, 5 - 7 hoursafter intravesical instillation of ALA solution, thefluorescence intensity of PpIX in the urothelium wasdoubled whilst in the muscle layer it remained low at asimilar level to those seen without the iron chelator.With CP94, further reduction of skin photosensitizationis possible as a similar photodynamic effect on thebladder could be achieved at lower ALA concentration.The addition of CP94 seems an effective and convenientway to potentiate ALA induced PpIX tissue selectivity.!27