Effects of Deuteration of C-Enriched Phospholactate on Efficiency of Parahydrogen-Induced Polarization by Magnetic Field Cycling.

We report herein a large-scale (>10 g) synthesis of isotopically enriched 1-C-phosphoenolpyruvate and 1-C-phosphoenolpyruvate-d for application in hyperpolarized imaging technology. The 1-C-phosphoenolpyruvate-d was synthesized with 57% overall yield (over two steps), and >98% H isotopic purity, representing an improvement over the previous report. The same outcome was achieved for 1-C-phosphoenolpyruvate. These two unsaturated compounds with C=C bonds were employed for parahydrogen-induced polarization via pairwise parahydrogen addition in aqueous medium. We find that deuteration of 1-C-phosphoenolpyruvate resulted in overall increase of H T of nascent hyperpolarized protons (4.30 ± 0.04 s versus 2.06 ± 0.01 s) and H polarization (~2.5% versus ~0.7%) of the resulting hyperpolarized 1-C-phospholactate. The nuclear spin polarization of nascent parahydrogen-derived protons was transferred to 1-C nucleus via magnetic field cycling procedure. The proton T increase in hyperpolarized deuterated 1-C-phospholactate yielded approximately 30% better C polarization compared to non-deuterated hyperpolarized 1-C-phospholactate. Analysis of T relaxation revealed that deuteration of 1-C-phospholactate may have resulted in approximately 3-fold worse H→C polarization transfer efficiency via magnetic field cycling. Since magnetic field cycling is a key polarization transfer step in the Side-Arm Hydrogenation approach, the presented findings may guide more rationale design of contrast agents using parahydrogen polarization of a broad range of C hyperpolarized contrast agents for molecular imaging employing C MRI. The hyperpolarized 1-C-phospholactate-d is of biomedical imaging relevance because it undergoes in vivo dephosphorylation and becomes C hyperpolarized lactate, which as we show can be detected in the brain using C hyperpolarized MRI; an implication for future imaging of neurodegenerative diseases and dementia.