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Abstract #3596

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

A novel treatment approach for glioblastoma is based on mesenchymal stem cell (MSC)-mediated gene therapies whereby cell accumulation can be influenced by the tumor microenvironment. Here, we demonstrate the ability to image pH, metabolic pyruvate-lactate conversion and hypoxia in glioblastoma using hyperpolarized [1,5-13C2,3,6,6,6-D4]zymonic acid-MRSI, [1-13C]pyruvate-MRI and [18F]FMISO-PET as predictors for hypoxia-targeted sodium-iodide-symporter (NIS)-expression of tumor-infiltrating MSCs assessed by 124I-PET. Observed hypoxia (SUVmean = 0.49±0.05) was confirmed by histology and occurred together with increased lactate-production (AUCmean = 1.14±0.17) and mild acidification (pHmean = 7.34±0.02). This shows to be a suitable environment for NIS-MSC-activity, thereby allowing efficient therapy.

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