ParaHydrogen Polarized Ethyl-[1-13 C]pyruvate in Water, a Key Substrate for Fostering the PHIP-SAH Approach to Metabolic Imaging.

Abstract

An efficient synthesis of vinyl‐[1‐13C]pyruvate has been reported, from which 13C hyperpolarized (HP) ethyl‐[1‐13C]pyruvate has been obtained by means of ParaHydrogen Induced Polarization (PHIP). Due to the intrinsic lability of pyruvate, which leads quickly to degradation of the reaction mixture even under mild reaction conditions, the vinyl‐ester has been synthesized through the intermediacy of a more stable ketal derivative. 13C and 1H hyperpolarizations of ethyl‐[1‐13C]pyruvate, hydrogenated using ParaHydrogen, have been compared to those observed on the more widely used allyl‐derivative. It has been demonstrated that the spin order transfer from ParaHydrogen protons to 13C, is more efficient on the ethyl than on the allyl‐esterdue to the larger J‐couplings involved. The main requirements needed for the biological application of this HP product have been met, i. e. an aqueous solution of the product at high concentration (40 mM) with a good 13C polarization level (4.8 %) has been obtained. The in vitro metabolic transformation of the HP ethyl‐[1‐13C]pyruvate, catalyzed by an esterase, has been observed. This substrate appears to be a good candidate for in vivo metabolic investigations using PHIP hyperpolarized probes.