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

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

doi:10.1016/j.jmro.2023.100129

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

Journal Article · Thu Jul 13 00:00:00 EDT 2023 · Journal of Magnetic Resonance Open

DOI:https://doi.org/10.1016/j.jmro.2023.100129· OSTI ID:2341420

MacCulloch, Keilian ^[1]; Browning, Austin ^[2]; Guarin Bedoya, David O. ^[3]; McBride, Stephen J. ^[2]; Abdulmojeed, Mustapha B. ^[2]; Dedesma, Carlos ^[4]; Goodson, Boyd M. ^[5]; Rosen, Matthew S. ^[3]; Chekmenev, Eduard Y. ^[6]; Yen, Yi-Fen ^[3]; TomHon, Patrick ^[4]; ^[2]

North Carolina State University, Raleigh, NC (United States); North Carolina State University
North Carolina State University, Raleigh, NC (United States)
Massachusetts General Hospital, Charlestown, MA (United States). Athinoula A. Martinos Center for Biomedical Imaging
Vizma Life Sciences Inc., Chapel Hill, NC (United States)
Southern Illinois Univ., Carbondale, IL (United States)
Wayne State Univ., Detroit, MI (United States). Integrative Bio-sciences (Ibio) and Karmanos Cancer Institute (KCI); Russian Academy of Sciences (RAS), Moscow (Russian Federation)

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.

View Accepted Manuscript (DOE)

Research Organization:: North Carolina State University, Raleigh, NC (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER); National Science Foundation (NSF); National Institutes of Health (NIH)

Grant/Contract Number:: SC0023334

OSTI ID:: 2341420

Journal Information:: Journal of Magnetic Resonance Open, Journal Name: Journal of Magnetic Resonance Open Vol. 16-17; ISSN 2666-4410

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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

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References (76)

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