Reduction of Muscle-Invasive Tumors by Photodynamic Therapy with Tetrahydroporphyrin-Tetratosylat in an Orthotopic Rat Bladder Cancer Model

Abstract

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. PDT (0-50 mmol/L THPTS; 10 J/cm 2 ) induced early onset of apoptosis leading to dose-dependent cytotoxicity in AY-27 cells. Singletime transurethral THPTS-PDT (100 mmol/L THPTS; 10 J/cm 2 ) 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) 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.

Evaluation of a Luminometric Cell Counting System in Context of Antimicrobial Photodynamic Inactivation

“…Based on data from previous studies, the illumination at the indicated doses should be well-tolerated by eukaryotic cells [ 45 , 46 , 47 ]. However, our in vitro study cannot rule out adverse effects of aPDI in adjacent host tissues.…”

Photodynamic Therapy for Bladder Cancers, A Focused Review†

“…Among those, Chlorin e4 was found to kill about 82% and 85% of cells when tried against T24 and 5637 bladder cancer cells In vitro (81). Another photosensitizer, tetrahydroporphyrin‐tetratosylat (THPTS), excites at 760 nm, which can penetrate up to 15 mm, was tried in rat orthotopic muscle invasive bladder cancer and achieved 60% tumor reduction compared with control at two weeks after PDT (82, 83) (Table 1).…”

Immunomodulatory Effects by Photodynamic Treatment of Glioblastoma Cells In Vitro

“…THPTS showed preferential accumulation in tumor cells of C26 colon carcinoma versus normal tissue, especially in mitochondria [ 30 , 31 ]. In vitro and in vivo studies already demonstrated the efficacy of THPTS-PDT, for example in a rat bladder cancer model and in human retinoblastoma cells [ 32 , 33 , 34 ]. Concerning GBM, in vitro studies proved a significant reduction of tumor cell clonogenicity by THPTS-PDT combined with IR, compared to single treatments.…”