Preclinical evaluation of 5-ALA based PDT for the treatment of canine urinary bladder cancer: fluorescence distribution and response of normal urinary bladder tissue

Photodynamic therapy (PDT) is a potential improvement over conventional therapy for urinary bladder cancer, especially using the pro-photosensitizer 5-aminolevulinic acid (ALA), which is metabolized to its active form, protoporphyrin IX (PpIX), within both normal and neoplastic epithelial tissue. The purpose of this study was to evaluate ALA-based PDT in healthy dogs as a prelude to treating dogs with transitional cell carcinoma of the urinary bladder. Methods: Twelve dogs were given oral ALA at 0, 30, 60, or 90 mg/kg. Four hours later, the dogs were sacrificed and bladder tissue was collected and frozen for low-intensity fluorescence microscopy. Fifteen dogs were given oral ALA at 0, 30, 60, or 90 mg/kg and anesthetized four hours later. The trigone was irradiated with 635 nm laser light. All dogs were necropsied after PDT (48 h or 21 d). Results: PpIX fluorescence was confined to the urinary bladder mucosa with no detectable fluorescence in the muscularis or serosa. Histopathological lesions after PDT were limited to mild inflammation. Conclusions: Oral ALA appears to be well tolerated by healthy dogs at the dosages used. Because PpIX fluorescence was confined to the mucosa, ALA-based PDT may be a useful treatment for canine lower urinary tract neoplasia.