Synthesis of 13 C and 2 H Labeled Vinyl Pyruvate and Hyperpolarization of Pyruvate.

The hyperpolarization of nuclear spins has enabled unique applications in chemistry, biophysics, and particularly metabolic imaging. Parahydrogen-induced polarization (PHIP) offers a fast and cost-efficient way of hyperpolarization. Nevertheless, PHIP lags behind dynamic nuclear polarization (DNP), which is already being evaluated in clinical studies. This shortcoming is mainly due to problems in the synthesis of the corresponding PHIP precursor molecules. The most widely used DNP tracer in clinical studies, particularly for the detection of prostate cancer, is 1-13 C-pyruvate. The ideal derivative for PHIP is the deuterated vinyl ester because the spin physics allows for 100 % polarization. Unfortunately, there is no efficient synthesis for vinyl esters of ß-ketocarboxylic acids in general and pyruvate in particular. Here, we present an efficient new method for the preparation of vinyl esters, including 13 C labeled, fully deuterated vinyl pyruvate using a palladium-catalyzed procedure. Using 50 % enriched parahydrogen and mild reaction conditions, a 13 C polarization of 12 % was readily achieved; 36 % are expected with 100 % pH2 . Higher polarization values can be potentially achieved with optimized reaction conditions.

Parahydrogen-induced polarization and spin order transfer in ethyl pyruvate at high magnetic fields.

Nuclear magnetic resonance has experienced great advances in developing and translating hyperpolarization methods into procedures for fundamental and clinical studies. Here, we propose the use of a wide-bore NMR for large-scale (volume- and concentration-wise) production of hyperpolarized media using parahydrogen-induced polarization. We discuss the benefits of radio frequency-induced parahydrogen spin order transfer, we show that 100% polarization is theoretically expected for homogeneous B0 and B1 magnetic fields for a three-spin system. Moreover, we estimated that the efficiency of spin order transfer is not significantly reduced when the B1 inhomogeneity is below ± 5%; recommendations for the sample size and RF coils are also given. With the latest breakthrough in the high-yield synthesis of 1-13C-vinyl pyruvate and its deuterated isotopologues, the high-field PHIP-SAH will gain increased attention. Some remaining challenges will be addressed shortly.