Aminolevulinic acid (ala) as a prodrug in photodynamic therapy of cancer

Abstract

Aminolevulinic acid (ALA) is an endogenous metabolite normally formed in the mitochondria from succinyl-CoA and glycine. Conjugation of eightALA molecules yields protoporphyrin IX (PpIX) and finally leads to formation ofheme. Conversion of PpIX to its downstream substrates requires the activityof a rate-limiting enzyme ferrochelatase. When ALA is administered externally the abundantly produced PpIX cannot be quickly converted to its final product - heme by ferrochelatase and therefore accumulates within cells. Since PpIX is a potent photosensitizer this metabolic pathway can be exploited in photodynamic therapy (PDT). This is an already approved therapeutic strategy making ALA one of the most successful prodrugs used in cancer treatment. © 2011 by the authors.