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Production of biocompatible 13C-hyperpolarized metabolic contrast agents at a gas-solid-interface

Subject Area Physical Chemistry of Molecules, Liquids and Interfaces, Biophysical Chemistry
Term from 2019 to 2023
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 418416679
 
Final Report Year 2023

Final Report Abstract

Para-hydrogen is a spin isomer of hydrogen gas, which can be used in nuclear magnetic resonance (NMR) to temporarily enhance signals by several orders of magnitude. The classical way is to perform a hydrogenation reaction using a catalyst in solvent. Over the past years, the use of para-hydrogen for the signal enhancement of metabolic molecules has become one focus, as it promises to be used as a contrast agent for biomedical imaging. In this regard, this technique has the advantage of being able to enhance the signal of metabolites in a few seconds, which is much faster than the state-of-the-art, dynamic nuclear polarization (DNP), which requires several 10 minutes to hours to do so. In the course of the investigation in this project, pure solutions of signal-enhanced - or hyperpolarized - metabolites were planned to be produced in order to test them in the context of cellular experiments. The aim was to investigate how precursor molecules of metabolites can be hydrogenated at a solid-gas interface and subsequently hydrolyzed to obtain the desired hyperpolarized metabolite. Early in the project, initial experiments were conducted with decorated nanocatalysts heated in an oven. In initial test experiments, propylene was hydrogenated, and it became apparent quite early in the project that not enough polarization was achieved to perform metabolism experiments. It was therefore subsequently focused on first developing pulsed NMR experiments to generate high concentration of metabolites in organic solvents that could be used for biological experiments. High concentration (50 mM) and very high polarization values (>10% on 13C spins of metabolites) could be obtained. This was subsequently used to perform cellular studies in Parkinson's disease and cancer models, particularly investigating pyruvate-lactate metabolism and its changes in disease. Ultimately, the developments made here provided a major contribution to the very first successful tumor images taken by us with para-hydrogen generated metabolites.

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