Abstract B14: Characterization of an orthotopic glioblastoma in vivo mouse model with firefly luciferase expressing human U87 cells using in vivo bioluminescence imaging and magnetic resonance imaging (MRI).
Authors: Lingnau Andreas , Hoffmann Steffen , Weidensteiner Claudia , Reichardt Wilfried , Kording Fabian , Esser Norbert , Niedermann Gabriele , Schaechtele Christoph 
Published: June 2012

Glioblastoma is the most common and most aggressive type of malignant brain tumors. The prognosis is poor, with a median survival time of several months only. Despite steady progress in treatment of glioblastomas this tumor entity is still not curable. Thus, there is an urgent need for the development of novel effective therapies, and for appropriate in vivo models to characterize them. Most often novel antiglioblastoma drugs are tested in subcutaneous xenograft mouse models using various human or murine glioblastoma cell lines. To generate more relevant, orthotopic brain cancer in vivo models, we stably transduced the human glioblastoma cell line U-87 with fire fly luciferase (U-87-Luci) suitable for in vivo bioluminescence imaging.

To initiate orthotopic growth, nude mice were anesthetized and placed in a stereotactic fixation device. Through a burr hole cells were implanted intracranially using a Hamilton syringe. Once to twice a week we used bioluminescence imaging to continually monitor tumor growth in vivo. However, as magnetic resonance imaging (MRI) is the most relevant tool to monitor oncological therapy in glioblastomas clinically, we adapted this translational aspect and analysed the mice in parallel using a dedicated animal MRI System. MRI offers detailed information about growth characteristics, size, blood supply and interaction with the surrounding tissue of the tumor. To achieve this, we performed T2-weighted imaging, and diffusion weighted imaging (DWI) weekly to visualise the tumors as well as necrosis and edemas. To monitor the blood supply of the glioblastomas we performed dynamic contrast enhanced MR imaging (DCE-MRI). The use of both methods allowed independent and complementary characterization of the tumors.

Approximately four weeks after implantation, exponential growth of the orthotopic tumors was observed, and another two weeks later necropsy was done. In vivo bioluminescence imaging revealed only a very dominant signal in the region of the brain where the primary tumor was located. To address potential metastases in more detail we analysed a set of different resected organs and tissues for in vitro luciferase activity followed by extensive histological examination.

Currently, we test different known anti-glioblastoma agents in this orthotopic model to evaluate an antitumoral effect as well as a potential reduction of the edemas. Next, we plan to test carefully novel compounds in order to discover new generations of drugs suitable to help glioblastoma patients.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B14.