Rapid and Simple <sup>13</sup>C-Hyperpolarization by <sup>1</sup>H Dissolution Dynamic Nuclear Polarization Followed by an Inline Magnetic Field Inversion
Quentin Stern, Quentin Reynard-Feytis, Stuart J. Elliott, Morgan Ceillier, Olivier Cala, Konstantin L. Ivanov, Sami Jannin
Abstract
Dissolution dynamic nuclear polarization (dDNP) is a method of choice for preparing hyperpolarized 13 C metabolites such as 1- 13 C-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 13 C spins reaching polarizations of >50% in ∼1–2 h. Alternatively, 1 H spins are polarized before transferring their polarization to 13 C 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 1 H dDNP followed by inline adiabatic magnetic field inversion in the liquid state during the transfer. 1 H 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 1 H → 13 C 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 13 C polarization up to ∼17% for 3- 13 C-pyruvate and 13 C-formate. The instrumentation needed to perform this experiment in addition to a conventional dDNP polarizer is simple and readily assembled.