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Imaging pH, metabolism and hypoxia using hyperpolarized 13C-MRI and [18F]FMISO-PET to predict NIS expression in MSC gene therapy in glioblastoma
Martin Grashei1, Carolin Kitzberger2, Jason G. Skinner1, Sandra Sühnel1, Geoffrey J. Topping1, Elisabeth Bliemsrieder1, Christian Hundshammer1, Katja Steiger3, Peter J. Nelson4, Rainer Glaß5, Wolfgang Weber1, Christine Spitzweg2, and Franz Schilling1
1Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany, 2Medizinische Klinik und Poliklinik IV-Campus Großhadern, University Hospital of Munich, Ludwig-Maximilians-University Munich, Munich, Germany, 3Department of Pathology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany, 4Medizinische Klinik und Poliklinik IV, University Hospital of Munich, Ludwig-Maximilians-University Munich, Munich, Germany, 5Neurosurgical Research University Clinics, Ludwig-Maximilians-University Munich and Walter-Brendel-Centre of Experimental Medicine, Munich, Germany
Multimodal PET/MRI imaging in glioblastoma was performed to characterize pH, metabolic conversion and hypoxia. Here, hypoxia resulted in increased lactate production promoting mild tumor acidification which can be targeted by MSC-mediated NIS gene therapies.

a: Imaging study protocol showing the temporal sequence of the applied modalities and injected tracers.

b: Axial anatomical T2-weighted 1H-RARE-image of a mouse bearing a subcutaneous GBM2-tumor (ROI encircled by white line) and Gd‑doped [1-13C]lactate-phantom (white arrow) covered by gel.

c: ADC-map showing the fitted diffusion coefficients based on 16 b-value images.

d: Mean pH-map weighted by compartment-intensities in the corresponding voxel overlaid with anatomical image.

a: Axial [1-13C]lactate intensity image integrated over the range displayed in c overlaid with an anatomical image.

b: Axial [1-13C]pyruvate intensity image integrated over the range displayed in c overlaid with an anatomical image.

c: Signal time curves for [1-13C]pyruvate (blue) and [1-13C]lactate (red) with a 3D tumor ROI. Integration ranges for intensity images in a and b are displayed with dashed lines.