Signal-enhanced real-time magnetic resonance: Developing and testing tools to study cell metabolism in lymphoma cells

• Applicants: Dr. Stefan Glöggler; Professor Dr. Dieter Kube
• Subject Area: Physical Chemistry of Molecules, Liquids and Interfaces, Biophysical Chemistry
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 535031387

Signal-enhanced magnetic resonance is a unique tool to monitor realtime enzymatic reactions in living cells. The process of signal enhancement of hyperpolarization allows for boosting signals of 13C enriched metabolites by over 10 000-fold and helps overcoming sensitivity limitations in magnetic resonance. In recent years we have worked on maximizing the signal of the important metabolite pyruvate that can be used to probe the energy metabolism of cells. Compared to the previous state-of-the-art which requires 10s of minutes to an hour to enhance the signal of pyruvate we now achieve similar results within seconds. We demonstrated that feeding the rapidly signalenhanced metabolites to cells, its conversion to different transient metabolites can be obtained. Such information can otherwise hardly be obtained by conventional assays or molecular biology approaches. We now want to use this approach and develop more probes and obtain new insights into the dynamic metabolic wiring of cancer. Here we propose the novel strategy to produce new signal-enhanced metabolite probes, aiming to characterize similarities and differences of TCA-cycle metabolite conversion rates between subtypes of lymphoma cells and get first insight into some functional aspects and mechanism of lymphoma specific Pyr-Lac conversion, TCA-cycle dynamics and dynamic of interplay of glycolysis and TCA-cycle. With success of these planned experiments, we will contribute to the diversity of analytical approaches for cancer metabolomics studies and a general understanding of metabolic features of lymphoma. We envision to further develop our novel signal-enhanced magnetic resonance method with a view on clinical applications.

• DFG Programme: Research Grants