Improving the Catalyst Efficiency for Hyperpolarization of Pyruvate Derivatives by Means of Hydrogenative PHIP

Hyperpolarized pyruvate is the most widely used probe for metabolic imaging in magnetic resonance (MR). Parahydrogen induced polarization- side arm hydrogenation allows to generate it through the catalytic hydrogenation of pyruvate esters. Due to the transient nature of MR hyperpolarization and to the fact that in vivo applications require a high amount of hyperpolarized substrate, a concentrated product solution must be obtained in a few seconds, therefore a high catalyst concentration is needed. The homogeneous rhodium catalyst used for the reaction can be deactivated by the hydrogenation products (or substrates) and the substrate-to-catalyst ratio becomes even lower, especially for pyruvate esters. The addition of tris-phenyl phosphine to the hydrogenation mixture prevents the catalyst deactivation, when it is due to the hydrogenation product allyl pyruvate and the amount of catalyst needed to obtain a concentrated batch of hyperpolarized pyruvate ester has been reduced significantly. Following to hydrolysis and extraction of sodium pyruvate in aqueous phase, the concentration of the hyperpolarized metabolite has been increased to about 60 mM and ¹³C-MRI experiments have been carried out using different dilution of the hyperpolarized metabolite in water.