Indirect Detection of Enzymatic Processes by Hyperpolarized NMR: Temporal Information, Enhanced Spectral Resolution and Slow Spin Relaxation

Introduction Continuous efforts are invested in developing improved NMR techniques to characterize metabolism. Particularly pressing is the need to enhance NMR’s sensitivity. The last years have witnessed what promises to become a major development in this area, with the advent of ex situ dynamic nuclear polarization (DNP). The long transfer times needed by this ex situ approach imply that only sites with long T1s will retain a useful hyperpolarization; for this reason, DNP-enhanced studies have focused principally on non-protonated low-γ nuclei like C of carbonyls or N of quaternary amines. This study describes a new approach capable of endowing ex situ DNP with an indirect-detection capability, whereby controlled “aliquots” of the low-g-nuclide hyperpolarization are repeatedly transferred to neighboring protons using spatially-selective principles. This method maximizes the efficiency of the transfer, and provides the temporal dimension needed for carrying out spectral characterizations of metabolism. H MRS detection also implies maximum sensitivity and an oft-improved resolution. The usefulness of this new approach is illustrated with hyperpolarized measurements of two Choline related enzymatic reactions involved in cancer metabolism and neuronal transmission.