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

Abstract

A robust and selective late-stage deuteration methodology was applied to ¹³C-enriched amino and alpha hydroxy acids to increase spin–lattice relaxation constant T₁ for hyperpolarized ¹³C magnetic resonance imaging. For the five substrates with ¹³C-labeling on the C1-position ([1-¹³C]alanine, [1-¹³C]serine, [1-¹³C]lactate, [1-¹³C]glycine, and [1-¹³C]valine), significant increase of their T₁ was observed at 3 T with deuterium labeling (+26%, 22%, +16%, +25% and +29%, respectively). Remarkably, in the case of [2-¹³C]alanine, [2-¹³C]serine and [2-¹³C]lactate, deuterium labeling led to a greater than four fold increase in T₁. [1-¹³C,2-²H]alanine, produced using this method, was applied to in vitro enzyme assays with alanine aminotransferase, demonstrating a kinetic isotope effect.