BIOCHEMICAL BASIS OF 5-AMINOLEVULINIC ACID-INDUCED PROTOPORPHYRIN-IX ACCUMULATION - A STUDY IN PATIENTS WITH (PRE)MALIGNANT LESIONS OF THE ESOPHAGUS

Administration of 5-aminolaevulinic acid (ALA) leads to porphyrin accu mulation in malignant and premalignant tissues, and ALA is used as a p rodrug in photodynamic therapy (PDT). To understand the mechanism of p orphyrin accumulation after the administration of ALA and to investiga te whether ALA-induced protoporphyrin IX might be a suitable photosens itizer in Barrett's oesophagus and adenocarcinoma, we determined the a ctivities of porphobilinogen deaminase (PBG-D) and ferrochelatase (FC) in various malignant and premalignant as well as in normal tissues of the human oesophagus, A PDT power index for ALA-induced porphyrin acc umulation, the ratio of PBG-D to FC normalized for the normal squamous epithelium of the oesophagus, was calculated to evaluate intertissue variation in the ability to accumulate porphyrins. In malignant and pr emalignant tissue a twofold increased PBG-D activity and a marginally increased FC activity was seen compared with normal squamous epitheliu m. A significantly increased PDT power index in Barrett's epithelium a nd adenocarcinoma was found. Our results suggest that, after the admin istration of ALA, porphyrins will accumulate in a greater amount in Ba rrett's epithelium and adenocarcinoma of the oesophagus because of an imbalance between PEG-D and FC activities. The PDT power index here de fined might be a useful indicative parameter for predicting the suscep tibility of these tissues to ALA-PDT.