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

• Applicant: Dr. Stefan Glöggler
• Subject Area: Physical Chemistry of Molecules, Liquids and Interfaces, Biophysical Chemistry
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 418416679

Nuclear Magnetic Resonance (NMR) is a phenomenon which is widely used e.g. in medical imaging to improve diagnostic capabilities. Sensitivity, however, is limiting in many applications. One possibility to enhance NMR signals is to use hyperpolarized metabolites as contrast agents. Thereby, nuclear spin states are selectively overpopulated in metabolites, leading to enhanced signals that are more than four orders of magnitudes more intense than the normal/thermal signal. Hyperpolarized metabolites are subsequently injected in vivo and allow for the real-time detection of e.g. a tumor metabolism. As the metabolic behavior is different between healthy and malicious tissue, this can guide clinical diagnosis.Currently, techniques to perform these investigations, however, are out of reach for many health care and research institutions, due to high acquisition and maintenance costs for polarization setups. In this proposal we are planning to investigate a cost-efficient alternative with which biocompatible hyperpolarized contrast agents can be generated using para-hydrogen. Via hydrogenation, the para-hydrogen spin order is converted into observable magnetization in metabolite precursors, leading to strong signal enhancement in these precursors. A subsequent chemical reaction rapidly converts the precursor into the desired metabolite that can be utilized as contrast agent. The hydrogenation usually utilizes homogeneous catalysts that can hardly be removed from the metabolite solutions on the timescale of the experiment, leading to toxicity concerns. Here, we are planning to investigate the hydrogenation of suitable metabolite precursors at a gas-solid-interface, which yield gaseous hyperpolarized precursors that will be trapped in water and converted into the final metabolites. We are going to use solid nano-catalysts that promote the hydrogenation at the gas-solid-interface and we will therefore achieve a spatial separation between the catalyst and the trapped contrast agents. This will mitigate toxicity concerns. In cell experiments, we will show that the metabolites obtained (specifically acetate, lactate and pyruvate) become metabolized. Due to the rapid production of hyperpolarized metabolites, we will be able to detect metabolic changes in the cells that can be triggered at-will in real-time. Ultimately, with our proposed technique we will pave new pathways to detect and investigate metabolic processes.

• DFG Programme: Research Grants
• Co-Investigator: Dr. Salvatore Mamone