Studies on the porphyrin síntesis from ALA derivatives employed in vitro and in vivo

PEROTTI C, CASAS A, FUKUDA H, DI VENOSA G, SACCA P, MACROBERT A, BATLLE A

Viena, Austria

Congreso; 10 th Congress of the European Society for Photobology; 2003

European Society for Photobiology

The aim of this work was to test in vitro and in vivo the efficacy of the derivatives of 5-aminolevulinic acid (ALA): Hexyl-ALA (He-ALA), Undecanoyl-ALA and R,S-ALA-2-(hydroximethyl)tetrahydropyranyl-ALA (THP-ALA). The compounds were tested in a cell line derived from a murine mammary tumour, in explants of tumour and in vivo, after injection of the cells into mice. Porphyrin synthesis in cells from He-ALA was more efficient than from ALA. However, Undecanoyl-ALA and THP-ALA did not improved ALA perfomance. The different kinetics of potphyrin synthesis from the derivatives suggest different uptake mechanism. I.p. injection to mice of ALA derivatives, resulted in a 4-fold lower porphyrin concentrations in tumour compared to equimolar amounts of ALA administration. In tumour explants, porphyrin synthesis from He-ALAis similar to porphyrin synthesis from ALA, and THP-ALA induces 3.3 times lower porphyrins compared to ALA. Undecanoyl-ALA induces almost basal tetrapyrrol synthesis, indicating the correlation between both in vitro models. When ALA levels were measured in the unperfused tunour after ALA or ALA derivatives injections, these levels did not correlate with porphyrin synthesis. This, together with in vitro data, suggest the capillaries are playing an important role in the entry of ALA esters into the cell.