Hyperpolarization by Dissolution-DNP for in vivo applications

Despite significant technological advancements over the past decades, the sensitivity of NMR is limited by the low thermal nuclear spin polarization. At a typical imaging field strength of 1.5 T and room temperature, the 1H spins are polarized to only 5 ppm, and a signal increase of 200,000 is thus theoretically possible. For other nuclei bearing lower magnetic moments (1/4 for 13C and 1/10 for 15N, respectively, compared to 1H), the theoretical enhancement factor is proportionally greater. In addition, the sensitivity of these nuclei is further reduced by the low natural abundance of the NMR-active isotopes (1.1 % for 13C and 0.36 % for 15N, respectively).

Hyperpolarization by dissolution-DNP is a versatile method for creating concentrated solutions of strongly polarized spins in molecules in solution. The method has enabled a range of in vivo and in vitro applications that otherwise would not be possible. Recent technological and methodological advances towards reaching the highest nuclear polarizations will be discussed.

Our interest has mainly been to polarize biological molecules enriched with 13C in positions with long T1 to study in vivo metabolism in real time (Metabolic MR). The increased signal obtained by hyperpolarization allows the measurement of metabolism of specific biochemical pathways that report on disease. This could be of importance for the diagnosis of cancer and cardiovascular disease, as well as other diseases involving changes in the cellular biochemistry. A particularly interesting compound has been pyruvate, a key intermediate in energy metabolism. Recently, we published the first human data with hyperpolarized [1-13C]pyruvate in patients with prostate cancer, a first test of the clinical performance of this technology.

Acknowledgement: Danish National Research Foundation and GE Healthcare.