INTRAVESICAL INSTILLATION OF 5-AMINOLEVULINIC ACID - THE FLUORESCENT METABOLITE IS LIMITED TO UROTHELIAL CELLS

Objectives For photodynamic therapy 5-aminolevulinic acid is an attrac tive compound, since it is a physiologic endogenous substance, and its application in excess results in the accumulation of the metabolite p rotoporphyrin IX, a very effective photosensitizer. The topical applic ation of 5-aminolevulinic acid in the urinary bladder led to pronounce d fluorescence in neoplasias when excited with violet laser light duri ng cystoscopy. The aim of this study was the determination of the tran smural distribution of protoporphyrin IX in order to estimate potentia l efficacy and side effects of a therapeutic application of 5-aminolev ulinic acid. Methods. 5-Aminolevulinic acid was instilled prior to cys toscopy and biopsies were taken of lesions that were either fluorescin g or nonfluorescing. Fluorescence distribution was analyzed by fluores cence microscopy on cryostat sections prepared from 72 biopsy specimen s. In addition, multicellular spheroids grown from tumor cells and fib roblasts were exposed to 5-aminolevulinic acid and analyzed accordingl y. Results. Biopsy preparations showed that the fluorescence of protop orphyrin IX was limited to normal and neoplastic urothelial cells. Cli nical findings were supported by the in vitro data, which showed negat ive protoporphyrin IX fluorescence in fibroblasts. Conclusions. Thus, 5-aminolevulinic acid might be superior in selective accumulation to c onventional sensitizers known to localize also in endothelial cells of the tumor stroma. The data appear to hold great promise for 5-aminole vulinic acid in photodynamic diagnosis and therapy in bladder cancer, as phototoxicity will be limited to mucosal lesions. Bladder shrinkage due to photodamage of subepithelial structures even in case of high l ight doses is not expected.