ECE2016 Guided Posters Thyroid Cancer (10 abstracts)
Systemic epidermal growth factor receptor-targeted gene delivery using the theranostic sodium iodide symporter (NIS) gene in an advanced orthotopic tumor model
Sarah Urnauer 1 , Stephan Morys 2 , Andrea M Müller 1 , Rosel Oos 3 , Janette Carlsen 3 , Peter Bartenstein 3 , Ernst Wagner 2 & Christine Spitzweg 1
1Department of Internal Medicine II, University Hospital of Munich, Ludwig-Maximilians-University, Munich, Germany; 2Department of Pharmacy, Center of Drug Research, Pharmaceutical Biotechnology, Ludwig-Maximilans-University, Munich, Germany; 3Department of Nuclear Medicine, University Hospital of Munich, Ludwig-Maximilians-University, Munich, Germany.
The well characterized sodium iodide symporter (NIS) in its dual function as reporter and therapy gene displays an outstanding opportunity to target different cancer types allowing non-invasive imaging of functional NIS expression and therapeutic radionuclide application. We recently reported induction of tumor-selective accumulation and therapeutic efficacy of radioiodide after systemic non-viral epidermal growth factor receptor (EGFR)-targeted NIS gene delivery in a subcutaneous hepatocellular cancer (HuH7) xenograft tumor model.
As a next step towards clinical application, we investigated tumor specificity and transduction efficiency of EGFR-targeted polyplexes based on linear polyethylenimine (LPEI), polyethylene glycol (PEG), and the synthetic peptide GE11 as an epidermal growth factor receptor (EGFR)-specific ligand (LPEI-PEG-GE11) as systemic NIS gene delivery vehicles in an advanced orthotopic tumor model. HuH7 cells were injected directly into the liver leading to the development of orthotopic liver tumors, representing a clinically more relevant model, as it reflects the clinical situation more adequately including the tumor microenvironment. In vitro experiments with LPEI-PEG-GE11/NIS polyplexes had already demonstrated high levels of EGFR-specific transduction efficacy in HuH7 cells. Mice with orthotopic HuH7 liver carcinomas showed high tumoral levels of functional NIS protein expression 24 h after intravenous injection of LPEI-PEG-GE11/NIS as shown by 124I-PET/18F-TFB imaging and ex vivo biodistribution. In contrast, injection of control vectors (LPEI-PEG-Cys/NIS) did not result in specific iodide uptake.
In conclusion, our preclinical data confirm the enormous potential of EGFR-targeted synthetic polymers for systemic NIS gene delivery in an advanced orthotopic tumor model and open the exciting prospect of NIS-mediated radionuclide therapy in advanced disease.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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