Long-lived 15N Hyperpolarization and Rapid Relaxation as a Potential Basis for Repeated First Pass Perfusion Imaging - Marked Effects of Deuteration and Temperature

Deuteration of the exchangeable hydrogens of [N-15(2)]urea was found to prolong the T-1 of the N-15 sites to more than 3min at physiological temperatures. This significant increase in the lifetime of the hyperpolarized state of [N-15(2)]urea, compared to [C-13]urea - a pre-clinically proven perfusion agent, makes [N-15(2)]urea a promising perfusion agent. The molecular parameters that may lead to this profound effect were assessed by investigating small molecules with different molecular structures containing N-15 sites bound to labile protons and determining the hyperpolarized N-15 T-1 in H2O and D2O. Dissolution in D2O led to marked prolongation for all of the selected sites. In whole human blood, the T-1 of [N-15(2)]urea was shortened. We present a general strategy for exploiting the markedly longer T-1 outside the body and the quick decay in blood for performing multiple hyperpolarized perfusion measurements with a single hyperpolarized dose. Improved storage of the generated [N-15(2)]urea polarization prior to the contact with the blood is demonstrated using higher temperatures due to further T-1 prolongation.