Rapid and Simple ¹³C-Hyperpolarization by ¹H Dissolution Dynamic Nuclear Polarization Followed by an Inline Magnetic...

Dissolution dynamic nuclear polarization (dDNP) is a method of choice for preparing hyperpolarized ¹³C metabolites such as 1-¹³C-pyruvate used for in vivo applications, including the real-time monitoring of cancer cell metabolism in human patients. The approach consists of transferring the high polarization of electron spins to nuclear spins via microwave irradiation at low temperatures (1.0-1.5 K) and moderate magnetic fields (3.3-7 T). The solid sample is then dissolved and transferred to an NMR spectrometer or MRI scanner for detection in the liquid state. Common dDNP protocols use direct hyperpolarization of ¹³C spins reaching polarizations of >50% in ∼1-2 h. Alternatively, ¹H spins are polarized before transferring their polarization to ¹³C spins using cross-polarization, reaching polarization levels similar to those of direct DNP in only ∼20 min. However, it relies on more complex instrumentation, requiring highly skilled personnel. Here, we explore an alternative route using ¹H dDNP followed by inline adiabatic magnetic field inversion in the liquid state during the transfer. ¹H polarizations of >70% in the solid state are obtained in ∼5-10 min. As the hyperpolarized sample travels from the dDNP polarizer to the NMR spectrometer, it goes through a field inversion chamber, which causes the ¹H → ¹³C polarization transfer. This transfer is made possible by the J-coupling between the heteronuclei, which mixes the Zeeman states at zero-field and causes an antilevel crossing. We report liquid-state ¹³C polarization up to ∼17% for 3-¹³C-pyruvate and ¹³C-formate. The instrumentation needed to perform this experiment in addition to a conventional dDNP polarizer is simple and readily assembled.