In vitro and in vivo studies employing the ALA dendrimer aminomethane tris methyl ALA TFA salt

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

Cambridge, UK

Workshop; Tetrapyrrole discussion group; 2004

Photodynamic Therapy (PDT) is a treatment for malignant and certain non-malignant lesions that involves administration of a photosensitising drug. The use of 5-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX) has become one of the most active fields of PDT research. In an attempt to improve delivery of ALA to tissue, we have investigated a new derivative of ALA based on a branched dendron segment conjugated with multiple ALA residues. The aim of this work was to evaluate in vivo and in vitro the efficacy of this first generation dendritic ALA derivative, an aminomethane tris-methyl ALA TFA salt (3m-ALA), which contains three ALA residues, in terms of porphyrin synthesis compared to ALA. In LM3 cells, 3m-ALA induces similar porphyrin levels compared to equimolar concentrations of ALA. Although 3m-ALA is taken up with comparable efficiency to ALA, we found that there is only partial intracellular liberation of ALA from 3m-ALA in this cell line. However, in vivo, both systemic and topical administration of 3m-ALA to tumour-bearing mice induced higher porphyrin levels than the hexyl ester derivative of ALA in most tissues studied, although it was not possible to surpass the levels induced by ALA.