Deuteration of the exchangeable hydrogens of [ 15 N 2 ]urea was found to prolong the T 1 of the 15 N sites to more than 3 min at physiological temperatures. This significant increase in the lifetime of the hyperpolarized state of [ 15 N 2 ]urea, compared to [ 13 C]urea – a pre‐clinically proven perfusion agent, makes [ 15 N 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 15 N sites bound to labile protons and determining the hyperpolarized 15 N T 1 in H 2 O and D 2 O. Dissolution in D 2 O led to marked prolongation for all of the selected sites. In whole human blood, the T 1 of [ 15 N 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 [ 15 N 2 ]urea polarization prior to the contact with the blood is demonstrated using higher temperatures due to further T 1 prolongation.
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Harris et al. (2018) studied this question.
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