Photodynamic Therapy: regulation of porphyrin synthesis and hydrolysis from ALA esters

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

Munich, Alemania

Congreso; IPA 10th; 2005

International Photodynamic Association

Photodynamic therapy (PDT) is a tool for the treatment of certain cancerous and pre-cancerous conditions, involving the presence of a photosensitiser and light. The natural precursor of porphyrins 5-aminolaevulinic acid (ALA) has been extensively used as a pro-photosensitiser in PDT and in the detection of superficial malignancies. Because ALA is a polar compound, its inherently poor permeability has been enhanced by chemical esterification with aliphatic alcohols. Some of the ALA esters proved to be more efficient than ALA in terms of porphyrin synthesis when employed at low concentrations. In the present work we studied the nature of porphyrin synthesis regulation from the ALA esters Hexyl-ALA (He-ALA) and R, S-ALA-2-(hydroxymethyl) tetrahydropyranyl ester (THP-ALA) in an adenocarcinoma cell line. We found that He-ALA is incorporated into the cells at a higher rate and more quickly, followed by THP-ALA and ALA. Whereas on the other hand, both ALA and ALA esters efflux from the cells at the same rate mediated by passive diffusion. Although ALA entrance to the cell might be regulating porphyrin levels, ALA derivative uptake appears not to be a limiting factor. At high concentrations, the regulation of ALA conversion into porphyrins is driven by the enzyme porphobilinogenase, whereas ALA esters hydrolysis is regulated by esterases. As long as no ALA is consumed, no hydrolysis will take place and porphyrins are not necessary for this regulation. The key conclusion of this contribution is that the use of ALA esters has to be limited to low concentrations where no regulation takes place on porphyrin synthesis.