SP 4 - Try-IBD

Magnetic Resonance imaging tracers for the analysis of tryptophan metabolism in vitro and in vivo

Nuclear Magnetic Resonance (NMR) spectroscopy and Magnetic Resonance Imaging (MRI) are among the most successful methods in physics, chemistry, biology and medicine. In the life sciences, magnetic resonance (MR) is a unique tool in providing insights into the anatomy, function and metabolism non-invasively, in vivo and in 3D.
While MR is very powerful and versatile, many extremely promising applications are currently not possible simply because the signal to noise ratio (SNR) is too low. These applications include the real time monitoring of metabolism. To make these applications possible, a strong enhancement of the SNR is necessary.
The largest known reservoir of signal enhancement is the alignment or polarization (P) of nuclear spins. In equilibrium, no more than a few parts per million of all spins of a sample or organism effectively contribute to the MRI signal at ambient conditions. By increasing the polarization, P, signal enhancements of a few 100,000 – fold were achieved in vitro and in vivo. This method, called hyperpolarization (HP), has enabled entirely new applications. A recent example is the monitoring of cancer treatment by measuring metabolism with high spatial and temporal resolution in vivo (Aggarwal et al., 2015). HP holds the potential to revolutionize medical diagnostics and could drastically increase the precision on visualization disease related molecular events, as e.g. in chronic inflammatory conditions as IBD.
We will use and develop the hyperpolarization method based on on the spin order of parahydrogen (pH2). pH2 is normal hydrogen gas (H2) whose nuclear spins are in the so-called singlet state. pH2 can be produced in bulk at low cost, stored and used on demand. Para-Hydrogen Induced Polarization methods are faster, cost-efficient and allow continuous production of hyperpolarized agents.
The aim of the subproject is to develop low cost production of hyperpolarized MRI agents for the in vivo analysis of tryptophan metabolism as a new diagnostic tool in IBD. Based on previous insights into the role of tryptophan metabolism in IBD, we specifically aim to produce and apply hyperpolarized tryptophan and nicotinamide in vivo.