Mechanisms of 15N dissolution dynamic nuclear hyperpolarization decay (15N-HP-decay)

• Applicant: Andrey Pravdivtsev, Ph.D.
• Subject Area: Physical Chemistry of Molecules, Liquids and Interfaces, Biophysical Chemistry ; Medical Physics, Biomedical Technology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 555951950

Nuclear magnetic resonance was revolutionized when hyperpolarization technologies were introduced. Such technologies offered superior NMR spectroscopy with nmol/L sensitivity and magnetic resonance imaging of in vivo metabolism for polarized tracers. Such tracers have a high specificity to different diseases. Biochemical studies suggest that there must be many more tracers with a high specificity to a broad range of diseases. However, such tracers were not yet accessible for molecular MRI. We found that some of these tracers can be hyperpolarized to more than 30%, but no polarization was left after transfer from the polarizer to the imaging site. We found this effect, for example, in nicotinamide (a form of vitamin B3), pyridine, pyrazine, and metronidazole: the lifetime of the 1-15N polarization can vary in the range of 2 to 100 seconds depending on physical conditions: pH, temperature, and magnetic field. Recent data from the literature indicate that the same effect is observed for succinate and fumarate at low magnetic fields. Hence, sample transportation can drastically affect the observed polarization value. The fast relaxation of some tracers is part of the reason why many promising metabolites have not received (pre-)clinical applications so far. There are diverse reasons why the relaxation may be so rapid during transportation: interaction with paramagnetic impurities, rapid chemical exchange, or strong spin-spin interactions. Effects from all these contributions can be altered and controlled by changing pH, temperature, or magnetic field. In the first place, however, the mechanism of such relaxation must be well understood. Moreover, recently, we found that some additives can significantly, by a factor of 10-100x, increase the polarization and its lifetime. In this project, we will synthesize novel 15N labeled tracers for molecular MRI (i), and construct a magnetic field cycling system for high-resolution NMR (ii), which will enable us to investigate the 13C and 15N lifetime of the hyperpolarization as a function of pH, magnetic field, temperature, and chemical additives (iii). This data will help us better understand the relaxation mechanism and design a protocol to conserve valuable polarization using our novel additives. Finally, we will assess the utility of the 15N hyperpolarization by utilizing in vitro and in vivo models (iv). This project aims to improve the applicability of hyperpolarization technology by understanding the fundamental properties of nuclear spins – the nuclear spin relaxation.

• DFG Programme: Research Grants