Toward Cleavable Metabolic/pH Sensing "Double Agents" Hyperpolarized by NMR Signal Amplification by Reversible Exchange.

Abstract

We show the simultaneous generation of hyperpolarized 13 C-labeled acetate and 15 N-labeled imidazole following spin-relay of hyperpolarization and hydrolysis of the acetyl moiety on 1-13 C-15 N2 -acetylimidazole. Using SABRE-SHEATH (Signal Amplification by Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei), transfer of spin order occurs from parahydrogen to acetylimidazole 15 N atoms and the acetyl 13 C site (≈263-fold enhancement), giving rise to relatively long hyperpolarization lifetimes at 0.3 T (T1 ≈52 s and ≈149 s for 13 C and 15 N, respectively). Immediately following polarization transfer, the 13 C-labeled acetyl group is hydrolytically cleaved to produce hyperpolarized 13 C-acetate/acetic acid (≈140-fold enhancement) and 15 N-imidazole (≈180-fold enhancement), the former with a 13 C T1 of ≈14 s at 0.3 T. Straightforward synthetic routes, efficient spin-relay of SABRE hyperpolarization, and facile bond cleavage open a door to the cheap and rapid generation of long-lived hyperpolarized states within a wide range of molecular targets, including biologically relevant carboxylic acid derivatives, for metabolic and pH imaging.