BIODISTRIBUTION OF PROTOPORPHYRIN-IX IN RAT URINARY-BLADDER AFTER INTRAVESICAL INSTILLATION OF 5-AMINOLEVULINIC ACID

Purpose: Photodynamic therapy (PDT) has considerable potential for the treatment of superficial bladder neoplasia. Problems of detrusor musc le scarring and prolonged cutaneous photosensitivity with current phot osensitizers may be reduced by using the new photosensitizer precursor , 5-aminolevulinic acid (ALA). We studied the fluorescence distributio n of protoporphyrin IX (PpIX, the active derivative of ALA) in rat uri nary bladder after intravesical administration of ALA as the first ste p to undertaking PDT using locally administered ALA. Materials and Met hods: Solutions of varying concentrations of ALA and pH were given int ravesically to Wistar rats. The bladder was removed 1 to 24 hours late r for measurement of the tissue levels of PpIX by fluorescence microsc opy in the layers of the bladder wall. Results: The stability of the A LA solution steadily decreased as the pH was increased from 2.1 to 7. The best value was pH 5.5, at which the stability of the solution and the urothelial tolerance were both acceptable. The maximum PpIX fluore scence intensity ratio between urothelium and the underlying muscle la yer was 11 to 1. This was seen 5 hours after instillation of 1% ALA so lution at pH 5.5. A 10% ALA solution gave higher levels of PpIX in the urothelium, but less selectivity between layers. Conclusions: Under a ppropriate conditions, intravesical instillation of ALA can be used to sensitize the bladder urothelium with a ratio between urothelial and muscle concentrations of PpIX of up to 11:1.