Cristian Urla1, Sorin Armeanu-Ebinger, Jörg Fuchs, Guido Seitz. 1. Department of Pediatric Surgery and Pediatric Urology, University Children's Hospital Tübingen, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany, Cristian.Urla@med.uni-tuebingen.de.
Abstract
BACKGROUND: Surgery for rhabdomyosarcoma is challenging due to a lack of clear delineation between tumor and surrounding tissue. Mutilating surgery can be necessary in difficult tumor localizations. Therefore, novel diagnostic and therapeutic modalities are required. The aim of this study was to evaluate the in vivo tumor detection of RMS using fluorescence laparoscopy and to analyze the efficacy of hypericin-induced photodynamic therapy in a mouse model. METHODS: Seventeen NOD/LtSz-scid IL2Rγnull-mice were divided into four groups. In group 1, mCherry-expressing tumor cells and in group 2-4 non-transfected tumor cells were xenotransplanted. Three weeks later, one fluorochrome per group (ICG, ICG-cetuximab, hypericin) was injected. Fluorescence laparoscopy was carried out and tumors were resected using fluorescence guidance. In the hypericin group, photodynamic therapy was performed using blue light and apoptosis was evaluated by TUNEL test. RESULTS: A clear discrimination between healthy and tumor tissue was feasible by fluorescending properties with mCherry expressing tumor cells and after injection of hypericin. No fluorescence was detected in mice injected with ICG and ICG-labeled cetuximab. Hypericin photodynamic therapy induced apoptosis of tumor cells after exposure to blue light. CONCLUSIONS: Intraoperative photodynamic diagnosis was feasible using mCherry-transfected tumor cells or hypericin. Additionally, intraoperative photodynamic therapy was possible and effective.
BACKGROUND: Surgery for rhabdomyosarcoma is challenging due to a lack of clear delineation between tumor and surrounding tissue. Mutilating surgery can be necessary in difficult tumor localizations. Therefore, novel diagnostic and therapeutic modalities are required. The aim of this study was to evaluate the in vivo tumor detection of RMS using fluorescence laparoscopy and to analyze the efficacy of hypericin-induced photodynamic therapy in a mouse model. METHODS: Seventeen NOD/LtSz-scid IL2Rγnull-mice were divided into four groups. In group 1, mCherry-expressing tumor cells and in group 2-4 non-transfected tumor cells were xenotransplanted. Three weeks later, one fluorochrome per group (ICG, ICG-cetuximab, hypericin) was injected. Fluorescence laparoscopy was carried out and tumors were resected using fluorescence guidance. In the hypericin group, photodynamic therapy was performed using blue light and apoptosis was evaluated by TUNEL test. RESULTS: A clear discrimination between healthy and tumor tissue was feasible by fluorescending properties with mCherry expressing tumor cells and after injection of hypericin. No fluorescence was detected in mice injected with ICG and ICG-labeled cetuximab. Hypericin photodynamic therapy induced apoptosis of tumor cells after exposure to blue light. CONCLUSIONS: Intraoperative photodynamic diagnosis was feasible using mCherry-transfected tumor cells or hypericin. Additionally, intraoperative photodynamic therapy was possible and effective.
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