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 (SUV_mean = 0.49±0.05) was confirmed by histology and occurred together with increased lactate-production (AUC_mean = 1.14±0.17) and mild acidification (pH_mean = 7.34±0.02). This shows to be a suitable environment for NIS-MSC-activity, thereby allowing efficient therapy.

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