Enhancing MR-Sensitivity of 19F-biomarkers and PET-analogous 19F-labeled receptor ligands by parahydrogen-induced polarization
Medical Physics, Biomedical Technology
Final Report Abstract
Within this project we developed an automated experimental setup, which allowed stable and reproducible hyperpolarization at different magnetic fields. This was a prerequisite for the detailed analysis of the complex reaction chain during the SABRE hyperpolarization of 19F. The systematic investigation of different aspects of 19F hyperpolarization using SABRE led to several new and previously unknown insights with regards to possible hyperpolarization transfer mechanisms from 1H to 19F. The position of fluorine plays an important role as on the 3-position (e.g. 3-fluoropyridine stronger hyperpolarization was observed than on the 2-position (e.g. 2-fluoropyridine). The pH value and the solvents had a strong influence on transfer mechanisms. In some cases an H/D-exchange was observed in methanol and this led to a hyperpolarization transfer to the OH-group of methanol but not to 19F. For further analysis new water-soluble catalysts were synthesized and characterized. The water solubility of other catalysts, such as the Ir-IMes catalyst, which were previously reported as watersoluble after activation, could not be confirmed. Similarly, a few of the water-soluble pyridine derivatives analyzed showed no hyperpolarization at either 1H or 19F. Thus, SABRE-based hyperpolarization of pyridine derivatives in solvents remains an important field of research but it seems that biocompatible application will require new approaches. As a consequence we investigated the potential of another promising hyperpolarization technique (photo-CIDNP) known to allow hyperpolarizing 19F-labeled biomolecules such as tyrosine and its derivatives in water using riboflavin as a photosensitizer. Both molecules play important roles in plant, animal and human metabolism. As preliminary work we modified the standard experimental approach by replacing the expensive, difficult to handle and potentially harmful Argon-laser by low cost blue-light LEDs. The achieved hyperpolarization was strong enough to acquire for the first time a 19F MR image of a photo-CIDNP hyperpolarized compound in aqueous solution using clinically applicable imaging sequences.
Publications
- Dipolar Induced Para-Hydrogen-Induced Polarization, Solid State Nuclear Magnetic Resonance, 2014, 63-64, 20-29
G. Buntkowsky, T. Gutmann, M.V. Petrova, K.L. Ivanov, U. Bommerich, M. Plaumann, J. Bernarding
(See online at https://doi.org/10.1016/j.ssnmr.2014.07.002) - Evidence for an intrinsic binding force between dodecaborate dianions and receptors with hydrophobic binding pockets, Chem. Commun., 2016, 52, 6300-6303
J. Warneke, C. Jenne, J. Bernarding, V. A. Azov, M. Plaumann
(See online at https://doi.org/10.1039/C6CC01233G) - SQUID-based detection of ultra-low-field multinuclear NMR of substances hyperpolarized using signal amplification by reversible exchange, Scientific Reports, 2017, 7, Art. Nr. 13431
K. Buckenmaier, M. Rudolph, C. Back, T. Misztal, U. Bommerich, P. Fehling, D. Koelle, R. Kleiner, H. A. Mayer, K. Scheffler, J. Bernarding, M. Plaumann
(See online at https://doi.org/10.1038/s41598-017-13757-7) - Low-cost LED-based photo-CIDNP enables biocompatible hyperpolarization of 19F for NMR and MRI at 7 T and 4.7 T, ChemPhysChem, 2018, 19(19), 2453-2456
J. Bernarding, F. Euchner, C. Bruns, R. Ringleb, D. Müller, T. Trantzschel, J. Bargon, U. Bommerich, M. Plaumann
(See online at https://doi.org/10.1002/cphc.201800570) - Mutual benefit achieved by combining ultralow-field magnetic resonance and hyperpolarizing techniques. Review of Scientific Instruments, 2018, 89, 125103
K. Buckenmaier, M. Rudolph, P. Fehling, T. Steffen, C. Back, R. Bernard, R. Pohmann, J. Bernarding, R. Kleiner, D. Koelle, M. Plaumann, K. Scheffler
(See online at https://doi.org/10.1063/1.5043369) - On the influence of the heterocyclic carbene ligand symmetry of Ir complexes on their performance for NMR signal amplification (SABRE), Applied Magnetic Resonance, 2019
S. Hadjiali, R. Savka, M. Plaumann, U. Bommerich, S. Bothe, T. Gutmann, T. Ratajczyk, J. Bernarding, H.-H. Limbach, H. Plenio, G. Buntkowsky
(See online at https://doi.org/10.1007/s00723-019-01115-x)
