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, 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 macroscopy and histology. Temperature-dependent THPTS uptake resulted in endosomal/lysosomal localization. PDT (0-50 µM THPTS; 10 J/cm2) induced early onset of apoptosis leading to dose-dependent cytotoxicity in AY-27 cells. Single-time transurethral THPTS-PDT (100 µM THPTS; 10 J/cm2) in F344 rats led to significant reduction of muscle-invasive tumor number (2/10 vs. 7/10 in controls) and total tumor volume (60% reduction) two 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 muscle-invasive urothelial cancer. This approach possibly allows minimal-invasive bladder preserving treatment of bladder cancer without systemic side effects.

Molecular cancer therapeutics. 2019 Mar 01 [Epub ahead of print]

Mandy Berndt-Paetz, Philipp Schulze, Philipp C Stenglein, Annett Weimann, Qiang Wang, Lars-Christian Horn, Yasser M Riyad, Jan Griebel, Ralf Hermann, Annegret Glasow, Jens-Uwe Stolzenburg, Jochen Neuhaus

Department of Urology, Research Laboratories, University of Leipzig ., Department of Urology, Research Laboratories, University of Leipzig., Institute for Pathology, University of Leipzig., Leibniz Institute of Surface Engineering., Wilhelm Ostwald Institute for Physical and Theoretical Chemistry., Department of Radiation Therapy, University of Leipzig., Department of Urology, Universitätsklinikum Leipzig.

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