Parahydrogen-induced hyperpolarization of 13C labeled keto carboxylic acids for medical applications: synthesis, polarization transfer, 13C-MRI

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Arguably the most critical 3D imaging modalities in medicine are MRI and CT. MRI is gaining importance because it does not use ionizing radiation, and it allows visualization beyond just anatomic or structural imaging. Anomalies in metabolic processes are often reliable indicators of diseases at very early stages of illness before anatomical changes (e.g., tumors) are visible in structural imaging. However, MRI is notoriously insensitive, and metabolic imaging requires even higher signal-to-noise ratios than mere anatomical imaging. Hyperpolarization to date is probably the most promising approach to increase the sensitivity of NMR and MRI to a level where intermediates in metabolic pathways can be detected, and their concentration visualized with spatial resolution. Among a plethora of biomarkers, α-ketocarboxylic acids are key molecules because they are intermediates in energy metabolism pathways such as the citric acid cycle and glycolysis. Particularly the pyruvate/lactate conversion is known to be an instrumental indicator for early-stage cancer (Warburg effect). The ultimate goal of this research project is to provide the scientific and technological basis for in vivo molecular and metabolic imaging by MRI using the so-called parahydrogen-induced polarization (PHIP) method. Towards this end, we will develop a cost-efficient synthesis of 13C and 2H labeled vinyl esters of pyruvate and other derivates of α-ketocarboxylic acids as precursors for PHIP (goal 1), and we will design hardware and PHIP experiments in intermediate magnetic fields for the scalable and convenient production of pyruvate and other α-ketocarboxylic acids for 13C MRI (goal 2). In vivo experiments will be performed in collaboration with other groups independently from this project.