Late-stage deuteration of 13C-enriched substrates for T1 prolongation in hyperpolarized 13C MRI

A robust and selective late-stage deuteration methodology was applied to C-13-enriched amino and alpha hydroxy acids to increase spin-lattice relaxation constant T-1 for hyperpolarized C-13 magnetic resonance imaging. For the five substrates with C-13-labeling on the C1-position ([1-C-13]alanine, [1-C-13]serine, [1-C-13]lactate, [1-C-13]glycine, and [1-C-13]valine), significant increase of their T-1 was observed at 3 T with deuterium labeling (+26%, 22%, +16%, +25% and +29%, respectively). Remarkably, in the case of [2-C-13]alanine, [2-C-13]serine and [2-C-13]lactate, deuterium labeling led to a greater than four fold increase in T-1. [1-C-13,2-H-2]alanine, produced using this method, was applied to in vitro enzyme assays with alanine aminotransferase, demonstrating a kinetic isotope effect.