LIGHT-SABRE Hyperpolarizes 1-¹³C-Pyruvate Continuously without Magnetic Field Cycling

Abstract

Nuclear spin hyperpolarization enables real-time observation of metabolism and intermolecular interactions <i>in vivo</i>. 1-¹³C-pyruvate is the leading hyperpolarized tracer currently under evaluation in several clinical trials as a promising molecular imaging agent. Still, the quest for a simple, fast, and efficient hyperpolarization technique is ongoing. Here, we describe that continuous, weak irradiation in the audio-frequency range of the ¹³C spin at the 121 μT magnetic field (approximately twice Earth's field) enables spin order transfer from parahydrogen to ¹³C magnetization of 1-¹³C-pyruvate. These so-called LIGHT-SABRE pulses couple nuclear spin states of parahydrogen and pyruvate via the <i>J</i>-coupling network of reversibly exchanging Ir-complexes. Using ∼100% parahydrogen at ambient pressure, we polarized 51 mM 1-¹³C-pyruvate in the presence of 5.1 mM Ir-complex continuously and repeatedly to a polarization of 1.1% averaged over free and catalyst-bound pyruvate. The experiments were conducted at -8 °C, where almost exclusively bound pyruvate was observed, corresponding to an estimated 11% polarization on bound pyruvate. The obtained hyperpolarization levels closely match those obtained via SABRE-SHEATH under otherwise identical conditions. The creation of three different types of spin orders was observed: transverse ¹³C magnetization along the applied magnetic field, ¹³C <i>z</i>-magnetization along the main field <i>B</i> ₀, and ¹³C-¹H <i>zz</i>-spin order. With a superconducting quantum interference device (SQUID) for detection, we found that the generated spin orders result from ¹H-¹³C <i>J</i>-coupling interactions, which are not visible even with our narrow linewidth below 0.3 Hz and at -8 °C.