Basics of the photodynamic therapy (PDT) of bladder carcinoma using Tetrahydroporphyrin-Tetratosylate (THPTS)

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Bladder carcinoma is the third most frequent tumour in Germany. The estimated mortality rate is 6.4%. The therapy of the bladder carcinoma depends on the tumour grade and invasiveness. Surgical interventions are transurethral resection of superficial tumours (TURB) and radical cystectomy in case of advanced, invasive stages. In support of the TURB, photodynamic diagnosis (PDD) using aminolevulinate or hexaminolevulinate has been established. PDD has improved the detection and resection of visually unsuspicious superficial urothelial tumours. Those substances have also been used for photodynamic therapy (PDT). However, due to insufficient tissue penetration of excitation light and due to toxic side effects caused by high irradiation, the results were disappointing.Tetrahydroporphyrin-Tetratosylate (THPTS) is the first photosensitizer with photo-physical properties and high absorption at infrared wavelength of 760nm, which might be suitable to treat superficial and infiltrating tumours by PDT. Prerequisite for successful establishment of THPTS-PDT is the proof of toxicological safety and efficiency in an animal model and the elucidation of the mode of action in vitro. We want to address those questions using a rat bladder carcinoma model and cultured bladder carcinoma cell lines. Bladder carcinoma will be induced in the rat bladder by instillation of AY27 rat bladder carcinoma cells. The established bladder tumours will be treated by THPTS-PDT. The safety of THPTS-PDT will be examined in animal model by dose range finding experiments including evaluation of possible injury of healthy bladder tissue. Treatment efficiency will be verified by histological examination. The mode of action of THPTS-PDT will be examined in vitro using cultured rat cells, human normal bladder cells and bladder carcinoma cell lines. We will apply confocal microscopy, immunocytochemistry, cell vitality and apoptosis assays, and gene expression analysis.