Nitrogen-15 dynamic nuclear polarization of nicotinamide derivatives in biocompatible solutions

Abstract

Dissolution dynamic nuclear polarization (dDNP) increases the sensitivity of magnetic resonance imaging by more than 10,000 times, enabling in vivo metabolic imaging to be performed noninvasively in real time. Here, we are developing a group of dDNP polarized tracers based on nicotinamide (NAM). We synthesized 1- 15 N-NAM and 1- 15 N nicotinic acid and hyperpolarized them with dDNP, reaching (13.0 ± 1.9)% 15 N polarization. We found that the lifetime of hyperpolarized 1- 15 N-NAM is strongly field- and pH-dependent, with T 1 being as long as 41 s at a pH of 12 and 1 T while as short as a few seconds at neutral pH and fields below 1 T. The remarkably short 1- 15 N lifetime at low magnetic fields and neutral pH drove us to establish a unique pH neutralization procedure. Using 15 N dDNP and an inexpensive rodent imaging probe designed in-house, we acquired a 15 N MRI of 1- 15 N-NAM (previously hyperpolarized for more than an hour) in less than 1 s.