Reduction of muscle-invasive tumors by photodynamic therapy with Tetrahydroporphyrin-Tetratosylat in an orthotopic rat bladder cancer model.

Photodynamic therapy (PDT) is a promising option for minimal-invasive treatment of bladder cancer. Efficacy of PDT in muscle-invasive urothelial cancer is still hampered by low tissue penetration of most photosensitizers due to short excitation wavelength. The novel light reactive agent tetrahydroporphyrin-tetratosylat (THPTS) is excitable at near-infrared (760 nm), allowing tissue penetration of up to 15 mm. Here, we established an orthotopic rat bladder cancer model and examined the effects of THPTS-PDT on tumor growth in vivo, and analyzed molecular mechanisms in vitro. We examined pharmacokinetics and subcellular localization, and evoked cell death mode in cultured rat urothelial carcinoma cells (AY-27). We used female F344 Fischer rats for in vivo studies. Ten rats each were used for THPTS-PDT and light-only control. Bladders were evaluated by macro- scopy and histology.'Temperature-dependent THPTS uptake resulted in endosomal/lysosomal localization. Mr (050 mu mol/LTHPTS; 10 J/cm(2)) induced early onset of apoptosis leading to dose-dependent cytotoxicity in AY-27 cells. Singletime transureth ralll THPTS-PDT (100 mu mol/L THPTS; 10J/cm(2)) in F344 rats led to significant reduction of musde-invasive tumor number (2/10 vs. 7/10 in controls) and total tumor volume (60% reduction) 2 weeks after PDT, while sparing healthy tissue. Here, we report for the first time effective tumor growth control by PDT in vivo. THPTS is a promising new photosensitizer with the advantage of higher therapeutic depth and the potential of high-selective therapy in muscleinvasive urothelial cancer. This approach possibly allows minimal-invasive bladder preserving treatment of bladder cancer without systemic side effects.