5-AMINOLEVULINIC ACID (ALA)-INDUCED PROTOPORPHYRIN-IX FLUORESCENCE AND PHOTODYNAMIC EFFECTS IN THE RAT BLADDER - AN IN-VIVO STUDY COMPARINGORAL AND INTRAVESICAL ALA ADMINISTRATION

Background and Objective: Photodynamic therapy (PDT) using 5-aminolevu linic acid (ALA)-induced protoporphyrin IX (PpIX) for sensitization is a promising treatment for carcinoma in situ and diffuse premalignant changes of the bladder. We studied the biodistribution of PpIX in a ra nge of tissues with oral and intravesical routes of administration of ALA and compared the photodynamic effects on bladder and skin. Study D esign/Materials and Methods: Normal Wistar rats were given oral or int ravesical ALA and PpIX levels in the liver, kidney, skin, and bladder measured by fluorescence microscopy on tissue sections. At the time of maximum PpIX levels, the bladder and skin on the back were illuminate d with light at 630 nm and the PDT effects compared. Results: PpIX flu orescence in the urothelium after 200 mg/kg given intravesically was c omparable to that found after 100 mg/kg orally. The ratio of PpIX leve ls between the urothelium and the underlying muscle was the same for b oth routes of administration, although there appeared to be more selec tivity of urothelial PDT necrosis after intravesical administration. S kin photosensitization was greater after oral ALA, the epidermal PpIX level being three times higher than after intravesical administration for comparable urothelial levels and the PDT effect being more marked. Conclusions: Intravesical instillation is preferable to oral administ ration of ALA for PDT ablation of the urothelium of the rat bladder wi thout damage to the underlying tissue layers and for minimizing skin p hotosensitivity. The technique is now ready for clinical trials. (C) 1 997 Wiley-Liss, Inc.