PURPOSE: To optimize photodynamic therapy (PDT) we investigated the kinetics and biodistribution of hexylester 5-aminolevulinate (hALA) induced protoporphyrin IX (PpIX) and the therapeutic efficacy of PDT at different drug and light doses in an orthotopic rat bladder tumor model. MATERIALS AND METHODS: Healthy and tumor bearing rats were instilled intravesically with hALA (4, 8 and 16 mM) for 1 hour. Fluorescence was recorded spectroscopically in situ. PpIX fluorescence distribution and quantification across the bladders was visualized with fluorescence microscopy. PDT efficacy at different fluences (15 to 80 J/cm2) was histologically assessed 48 hours and 1 week after treatment. RESULTS: Spectroscopic analysis in normal or tumor bearing rats showed the highest tumor-to-normal ratios 2 or 3 hours after the end of the 8 or 16 mM hALA instillation (5.4 and 5.7, respectively). Within the same tumor bearing animal the same fluorescence levels were observed in normal epithelium and transitional cell carcinoma, whereas the tumor-to-muscle ratio was 3. Tumor necrosis with an intact normal bladder wall was observed with a fluence of 20 J/cm2 for 8 mM hALA, while 15 J/cm2 was ineffective and 25 J/cm2 induced total wall necrosis. Although it induced comparable PpIX fluorescence, 16 mM hALA did not result in tumor eradication at any fluence. CONCLUSIONS: An optimal PDT effect was obtained with 8 mM hALA and a fluence of 20 J/cm2. While different hALA concentrations ind uce identical PpIX fluorescence intensities, the PDT outcome was considerably different. Thus, fluorescence does not necessarily predict the therapeutic efficacy of PDT.
PURPOSE: To optimize photodynamic therapy (PDT) we investigated the kinetics and biodistribution of hexylester 5-aminolevulinate (hALA) induced protoporphyrin IX (PpIX) and the therapeutic efficacy of PDT at different drug and light doses in an orthotopic ratbladder tumor model. MATERIALS AND METHODS: Healthy and tumor bearing rats were instilled intravesically with hALA (4, 8 and 16 mM) for 1 hour. Fluorescence was recorded spectroscopically in situ. PpIX fluorescence distribution and quantification across the bladders was visualized with fluorescence microscopy. PDT efficacy at different fluences (15 to 80 J/cm2) was histologically assessed 48 hours and 1 week after treatment. RESULTS: Spectroscopic analysis in normal or tumor bearing rats showed the highest tumor-to-normal ratios 2 or 3 hours after the end of the 8 or 16 mM hALA instillation (5.4 and 5.7, respectively). Within the same tumor bearing animal the same fluorescence levels were observed in normal epithelium and transitional cell carcinoma, whereas the tumor-to-muscle ratio was 3. Tumor necrosis with an intact normal bladder wall was observed with a fluence of 20 J/cm2 for 8 mM hALA, while 15 J/cm2 was ineffective and 25 J/cm2 induced total wall necrosis. Although it induced comparable PpIX fluorescence, 16 mM hALA did not result in tumor eradication at any fluence. CONCLUSIONS: An optimal PDT effect was obtained with 8 mM hALA and a fluence of 20 J/cm2. While different hALA concentrations ind uce identical PpIX fluorescence intensities, the PDT outcome was considerably different. Thus, fluorescence does not necessarily predict the therapeutic efficacy of PDT.