Facile hyperpolarization chemistry for molecular imaging and metabolic tracking of [1–13C]pyruvate in vivo

• Published in: Journal of Magnetic Resonance Open Vol. 16-17; p. 100129
• Main Authors: MacCulloch, Keilian, Browning, Austin, Guarin Bedoya, David O., McBride, Stephen J., Abdulmojeed, Mustapha B., Dedesma, Carlos, Goodson, Boyd M., Rosen, Matthew S., Chekmenev, Eduard Y., Yen, Yi-Fen, TomHon, Patrick, Theis, Thomas
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-12-2023; Elsevier
• Subjects: hyperpolarization; hyperpolarized imaging; Hyperpolarized MRI; in vivo imaging; INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Metabolic imaging; molecular imaging; Parahydrogen; pyruvate; RADIOLOGY AND NUCLEAR MEDICINE; SABRE; Hyperpolarized MRI; NMR; MRI; SABRE; HP; Parahydrogen; Metabolic imaging; PET; D-DNP
• ISSN: 2666-4410; 2666-4410
• DOI: 10.1016/j.jmro.2023.100129

•First demonstration of SABRE polarized [1–13C]pyruvate detected in vivo.•Metabolic conversion of pyruvate to lactate, alanine, and bicarbonate are observed.•Chemical Shift Imaging (CSI) is demonstrated in liver and in kidney.•Multiple site and multi field demonstrations.•Improved biocompatibility, avoiding methanol and catalyst in the injectables.
Hyperpolarization chemistry based on reversible exchange of parahydrogen, also known as Signal Amplification By Reversible Exchange (SABRE), is a particularly simple approach to attain high levels of nuclear spin hyperpolarization, which can enhance NMR and MRI signals by many orders of magnitude. SABRE has received significant attention in the scientific community since its inception because of its relative experimental simplicity and its broad applicability to a wide range of molecules, however, in vivo detection of molecular probes hyperpolarized by SABRE has remained elusive. Here we describe a first demonstration of SABRE-hyperpolarized contrast detected in vivo, specifically using hyperpolarized [1–13C]pyruvate. Biocompatible formulations of hyperpolarized [1–13C]pyruvate in, both, methanol-water, and ethanol-water mixtures followed by dilution with saline and catalyst filtration were prepared and injected into healthy Sprague Dawley and Wistar rats. Effective hyperpolarization-catalyst removal was performed with silica filters without major losses in hyperpolarization. Metabolic conversion of pyruvate to lactate, alanine, and bicarbonate was detected in vivo. Pyruvate-hydrate was also observed as a minor byproduct. Measurements were performed on the liver and kidney at 4.7 T via time-resolved spectroscopy and chemical-shift-resolved MRI. In addition, whole-body metabolic measurements were obtained using a cryogen-free 1.5 T MRI system, illustrating the utility of combining lower-cost MRI systems with simple, low-cost hyperpolarization chemistry to develop safe and scalable molecular imaging.
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