ENDOGENOUS PORPHYRIN DISTRIBUTION INDUCED BY 5-AMINOLEVULINIC ACID INTHE TISSUE LAYERS OF THE GASTROINTESTINAL-TRACT

The accumulation of endogenous porphyrins in rats following systemic a dministration of 5-aminolaevulinic acid (ALA) has been examined to ass ess the photosensitization characteristics of this technique for photo dynamic therapy (PDT) and chemical extraction assays with fluorescence and absorbance detection of the porphyrin content have been carried o ut. We compared the results obtained using quantitative microfluorimet ry on normal gastric and colonic tissues in rats at 0.5, 1, 2, 4 and 6 h and chemically induced duodenal tumours 2 and 4.5 h after intraveno us administration of ALA at a dose of 200 mg kg-1. With chemical extra ction followed by high performance liquid chromatography analysis, pro toporphyrin IX (PpIX) was found to be the predominant porphyrin presen t, reaching peak levels of several microgrammes per gramme at 2-4 h in each type of tissue; a small amount of coproporphyrin was detected at 0.5 and 2 h in normal gastric mucosa and duodenal tumour respectively . Both the extraction assay and quantitative microfluorimetry showed t hat the porphyrin fluorescence builds up rapidly in the mucosal layers of the colon and stomach, reaching a maximum at 2 h, whereas lower fl uorescence levels were found with a slower rate of accumulation in the corresponding muscularis layers. A significant PpIX content was found in the duodenal tumour, with a maximum of 7.1 mug g-1 4.5 h after AI- A administration. We conclude that systemic administration of ALA can induce effective tissue sensitization with protoporphyrin IX and appea rs to be a promising technique for PDT.