Photodynamic Therapy: ALA esters hydrolysis and porphyrin synthesis regulation

DI VENOSA G, FUKUDA H, MACROBERT A, CASAS A, BATLLE A.

Buenos Aires. Argentina

Workshop; 5th International Workshop on Photodynamic Therapy and Photodetection with Porphyrin Precursors; 2006

5-aminolevulinic acid (ALA), the natural precursor of biological porphyrins, is used as a pro-photosensitiser in PDT, to improve the treatment, ALA derivatives with chemical esterification with aliphatic alcohols have been synthesised. We have studied the nature of porphyrin synthesis regulation from the esters He-ALA and THP-ALA in the murine adenocarcinoma cell line LM3. We found that the rate of incorporation into the cells increase as ALA < THP-ALA < He-ALA. Although at low concentration, ALA uptake is a regulatory factor, this is not the case with ALA derivatives. At high concentrations, porphobilinogenase is regulating ALA conversion into porphyrins, while esterases regulate ALA-ester hydrolisis. In the presence of succinyl acetone, inhibitor of ALA-dehydratase, no changes in total ALA derivative intracellular accumulation or in the amount of hydrolysed ALA were observed. Our results suggest that the use of ALA-esters has to be limited to low concentrations where no regulation on porphyrin synthesis takes place.