Characterization of hypoxic tumor areas in high grade gliomas by means of simultaneous PET/MRT

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High-grade glioma are highly malignant, proliferating brain tumors, which tend to be hypoxic and diffusely infiltrate the surrounding healthy brain tissue. Hypoxia plays an important role with respect to differentiation of tumor stem cells, resistance to radiation therapy, neoangiogenesis and resulting cell proliferation. Notably, tumor hypoxia is closely correlated with a poor clinical patient outcome. Therefore, the aim of the proposed project is a comprehensive characterization of hypoxic brain tumor areas by means of a combined innovative hypoxia-sensitive magnetic resonance imaging (MRI) and positron emission tomography (PET) approach in untreated patients with tentative diagnosis of high-grade glioma. The main intention is to establish innovative multimodal hypoxia-related imaging biomarkers. Since tumor hypoxia may be subject to a high temporal and spatial variability, a novel method which allows simultaneous measurement of MR-based post-capillary venous oxygen saturation and PET-based intra-cellular hypoxia (using 18F-Fluoromisonidazole (18F-FMISO), will be applied on a new, combined PET/MRI scanner (SIEMENS Biograph mMR). Using an optimized PET-based delineation of the metabolic tumor volume, with the well-established amino acid radiotracer 18F-Fluorethylthyrosine (18F-FET), hypoxic tumor areas in the metabolic tumor volume are to be identified by the novel MRI and PET hypoxia markers. Additionally, targeted stereotactic tumor biopsies will be obtained in order to correlate MRI- and PET-hypoxia-measures with different immunohistochemistry markers of hypoxia. Finally, in a comprehensive appraisal of all results, the patient outcome will be evaluated on the basis of dichotomous hypoxia categorization.