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// Peter Hambsch 1 , Yury P. Istomin 3 , Dimitri A. Tzerkovsky 3 , Ina Patties 1 , Jochen Neuhaus 4 , Rolf-Dieter Kortmann 1 , Stanislav Schastak 2 and Annegret Glasow 1 1 Department of Radiation Therapy, University of Leipzig, 04103 Leipzig, Germany 2 Department of Ophthalmology, University of Leipzig, 04103 Leipzig, Germany 3 N. N. Alexandrov Republican Scientific and Practical Center of Oncology and Medical Radiology, 223040 Lesnoy, Republic of Belarus 4 Department of Urology, University of Leipzig, 04103 Leipzig, Germany Correspondence to: Annegret Glasow, email: Annegret.Glasow@medizin.uni-leipzig.de Keywords: photodynamic therapy, glioblastoma, THPTS, combination, ionizing radiation Received: January 10, 2017 Accepted: August 04, 2017 Published: August 23, 2017 ABSTRACT Background: So far, glioblastomas cannot be cured by standard therapy and have an extremely poor median survival of about 15 months. The photodynamic therapy (PDT) with next generation photosensitizers, reaching a higher therapeutic depth, might offer a new, adjuvant treatment strategy in brain cancer therapy. Here, we investigated the effect of THPTS-PDT combined with ionizing irradiation (IR) on glioblastoma cells in vitro and in vivo . Results: THPTS colocalized to mitochondria and was not found in the nucleus. THPTS (2–20 μg/ml)-PDT significantly reduced the proliferation, metabolic activity and clonogenic survival and induced cell death mainly through apoptosis and autophagy. THPTS-PDT combined with IR decreased the clonogenicity significantly compared to single treatments. THPTS (≤ 300 μg/ml) alone showed no dark toxicity. The maximum therapeutic depth of THPTS-PDT in C6 glioblastomas was 13 mm. Materials and Methods: Three human glioblastoma cell lines (U-87 MG, A-172, DBTRG-05MG) were incubated with THPTS (1–300 μg/ml) 3–24 hours before laser treatment (760 nm, 30 J/cm²). THPTS localization and effects on metabolic activity, proliferation, cell death mechanisms and long-term reproductive survival were assessed. IR was conducted on an X-ray unit (0.813 Gy/min). Results were verified in vivo on a subcutaneous C6 glioblastoma model in Wistar rats. Conclusions: This study demonstrated efficient THPTS-PDT in glioblastoma cells, in vitro and in vivo . The combinatorial effects of THPTS-PDT and IR are of specific clinical interest as enhanced eradication of infiltrating glioblastoma cells in the tumor surrounding tissue might possibly reduce the commonly occurring local relapses.