Deuteration enhances UV-induced hyperpolarization of [1-13C]pyruvate to trityl-level performance in vitro and in vivo.

Abstract

Dissolution dynamic nuclear polarization (dDNP) using UV-irradiated, non-persistent radicals has recently emerged as a filtration-free alternative to trityl-based methods; however, its performance for in vivo metabolic imaging remains insufficiently evaluated. Here, we systematically assessed UV-induced hyperpolarized (HP) [1-13C]pyruvate and its deuterated analog in the mouse brain, a technically demanding target for HP 13C MRI, and directly compared the results with conventional OX063-based dDNP. UV-induced HP [1-13C]pyruvate yielded lactate-to-pyruvate and bicarbonate-to-pyruvate ratios equivalent to those obtained with OX063-polarized preparations, and demonstrated good test-retest reproducibility. Deuteration substantially improved the polarization levels of UV-irradiated samples to values comparable to trityl-based dDNP, while preserving comparable in vivo metabolic readouts. Building on this methodological validation, awake 13C MRSI using HP [1-13C, d4]pyruvate, as applied in the present study, was used as a proof-of-concept in an Alzheimer's disease mouse model, where increased pyruvate-to-lactate conversion was detected in hippocampus-including regions of 3-month-old APPNL-G-F knock-in mice. Together, these results support UV-induced, deuterated HP pyruvate as a practical alternative to trityl-based dDNP and demonstrate its feasibility for preclinical HP 13C MRI studies of brain metabolism.