Hyperpolarized ¹⁵N caffeine, a potential probe of liver function and perfusion

AbstractPurposeTo demonstrate hyperpolarization of 15N‐caffeine and report exploratory findings as a potential probe of liver function and perfusion.MethodsAn amorphous formulation of [1,3‐15N2]caffeine was developed for hyperpolarization via dissolution dynamic nuclear polarization. Polarizer hardware was augmented to support monitoring of solid‐state 15N MR signals during the buildup of hyperpolarization. Liquid state hyperpolarized 15N MR signals were obtained in a preclinical 3T magnet by interfacing an external spectrometer console with home‐built RF surface coils. 15N signal decay constants were estimated in H2O and in vivo in liver and brain regions of rats at 3 T. Decays were also measured at 9.4 T to assess the effect of B0, and in the presence of albumin to assess the impact of protein binding.ResultsPolarization levels of 3.5% and aqueous T1 relaxation times of nearly 200 s were attained for both N1 and N3 positions at 3 T. Shorter apparent decay constants were observed in vivo, ranging from 25 s to 43 s, with modest extensions possible by exploiting competitive binding of iophenoxate with plasma albumin. Downstream products of caffeine could not be detected on in vivo 15N‐MR spectra of the liver region, even with metabolic stimulation by ‐naphthoflavone treatment. Considering the high perfusion rate of brain, persistence of caffeine signal in this region is consistent with potential value as a perfusion imaging agent.ConclusionThese results establish the feasibility of hyperpolarization of hyperpolarized 15N‐caffeine, but further work is necessary to establish the role of this new agent to probe liver metabolism and perfusion.