Biosynthesis and photodynamic efficacy of protoporphyrin IX (PpIX) generated by 5-aminolevulinic acid (ALA) or its hexylester (hALA) in rat bladder carcinoma cells

Hexylester of 5-aminolevulinic acid (hALA) has been considered as an altern ative to 5-aminolevulinic acid (ALA) for the treatment of malignancies of d ifferent origin. The present study addresses the ALA and hALA-induced PpIX pharmacokinetic profile using rat bladder carcinoma cells (AY27). The total PpIX content measured spectrofluorimetrically after extraction procedure a t the end of 2 h incubation was at least 1.5-fold greater with hALA compare d to ALA despite the difference in concentration of several orders between the two compounds (1 or 5 mM ALA and 5 or 10X10(-3) mM hALA). Considerable PpIX efflux was detected in the extracellular medium at the end of the incu bation. With 5 mM ALA and 10X10(-3) mM hALA, PpIX build-up was continued be yond the incubation period pointing out to enzyme saturation in the biosynt hetic pathway or/and the constitution of ALA reserve. Red laser light (lamb da =630 nm) irradiation of AY27 cells after 2 h incubation with increasing ALA or hALA concentrations resulted in a nearly equal photocytotoxicity. (C ) 2000 Elsevier Science B.V. All rights reserved.