Exchange facilitated indirect detection of hyperpolarized 15ND2-amido-glutamine

Hyperpolarization greatly enhances opportunities to observe in vivo metabolic processes in real time. Accessible timescales are, however, limited by nuclear spin relaxation times, and sensitivity is limited by magnetogyric ratios of observed nuclei. The majority of applications to date have involved direct C-13 observation of metabolites with non-protonated carbons at sites of interest (C-13 enriched carbonyls, for example), a choice that extends relaxation times and yields moderate sensitivity. Interest in N-15 containing metabolites is equally high but non-protonated sites are rare and direct N-15 observation insensitive. Here an approach is demonstrated that extends applications to protonated N-15 sites with high sensitivity. The normally short relaxation times are lengthened by initially replacing protons (H) with deuterons (D) and low sensitivity detection of N-15 is avoided by indirect detection through protons reintroduced by H/D exchange. A pulse sequence is presented that periodically samples N-15 polarization at newly protonated sites by INEPT transfer to protons while returning N-15 magnetization of deuterated sites to the +Z axis to preserve polarization for subsequent samplings. Applications to (ND2)-N-15-amido-glutamine are chosen for illustration. Glutamine is an important regulator and a direct donor of nitrogen in cellular metabolism. Potential application to in vivo observation is discussed. (C) 2011 Elsevier Inc. All rights reserved.