Project description: The altered metabolism of tumors can be monitored with nuclear magnetic resonance (NMR) spectroscopy using NMR-active metabolites. With the implementation of hyperpolarized 13C-molecules such as 13C–pyruvate, it has become possible to measure the metabolic dynamics within a few seconds. The evaluation of the NMR-signals requires knowledge on the influence of the tumor microenvironment on the cellular uptake of metabolites, especially on how nutrient and oxygen deprivation as well as an acidic pH modulate the cellular uptake of 13C-pyruvate. For this, 3D in-vitro tumor cell structures (spheroids) maintained in various tumor-like growth conditions serve as model systems. Further biochemical investigations will focus on 1) the cellular uptake of 14C-pyruvate, 2) the activity of metabolic enzymes, and 3) the metabolic flux of 13C-pyruvate using mass spectroscopy (isotopologue profiling). This project will be done in close cooperation with the Department of Biochemistry and the Clinic for Nuclear Medicine (Klinikum rechts der Isar) at the TUM.