Combined Homogeneous and Heterogeneous Hydrogenation with Parahydrogen to Yield Catalyst-Free Solutions of Hyperpolarized [1-13C]Succinate

We show that catalyst-free aqueous solutions of hyperpolarized [1-13C]succinate can be produced using parahydrogen-induced polarization (PHIP) and a combination of homogeneous and heterogeneous catalytic hydrogenation reactions. We generate hyperpolarized [1-13C]fumarate at 23% 13C polarization via PHIP with a homogeneous ruthenium catalyst, and subsequently remove the toxic catalyst and reaction side products via a purification procedure. Following this, we perform a second hydrogenation reaction to convert the fumarate into succinate using a solid Pd/Al2O3 catalyst. The catalyst is filtered off to yield a clean aqueous solution containing [1-13C]succinate at 11.9% 13C polarization for the hyperpolarized molecules. In this proof-of-principle demonstration we simplified the purification procedure by adding unpolarized fumarate to the mixtures so the observed succinate polarization was lower, but this step is not necessary for applications. This inexpensive polarization protocol has a turnover time of a few minutes, and represents a major advance for in vivo applications of [1-13C]succinate as a hyperpolarized contrast agent.