In vivo monitoring of hyperpolarized [15N]betaine-d11 signal for one hour

Dissolution dynamic nuclear polarization (DNP) is a technique that enhances the detection sensitivity of molecular probes in magnetic resonance imaging (MRI). DNP-MRI enables the detection of various biological parameters such as pH, perfusion, and metabolic reactions. However, the range of its applications is limited by the short lifetime of hyperpolarized probes. The detectable duration of in vivo hyperpolarized signal is ~10 min, i.e., within a minute timescale, which is insufficient to track in vivo events occurring on an hour timescale. Here, we report [15N]betaine-d11 as a DNP-MRI probe exhibiting extremely long hyperpolarization retention in vivo. The [15N]betaine-d11 effectively suppresses nuclear-spin relaxations and showed a very long spin-lattice relaxation time (T1 = 1,584 s, deuterated PBS, 1.4 T). Using this probe, we successfully monitored in vivo hyperpolarized 15N MR signals from a mouse body for approximately one hour. Furthermore, we detected the distribu-tion and accumulation of [15N]betaine-d11 for over 50 min in the tumor, where betaine plays a critical role.