Multidimensional pH-Temperature Mapping of SABRE-SHEATH 13 C Hyperpolarization of [1- 13 C]Pyruvate
Year: 2025
Type: article
Abstract: Hyperpolarized [1- 13 C]pyruvate has emerged as a next-generation molecular probe for in vivo metabolic flux imaging in deep tissue. This molecular contrast agent is now under evaluation in over 50 clinical trials, according to clinicaltrials.gov. Hyperpolarized [1- 13 C]pyruvate is produced through dissolution dynamic nuclear polarization (d-DNP) for clinical research use. This remarkable hyperpolarization technique is regarded as expensive (>$2 M equipment cost) and slow (1 h production). One alternative hyperpolarization technique called Signal Amplification By Reversible Exchange (SABRE) in SHield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH) has recently garnered substantial attention for production of hyperpolarized [1- 13 C]pyruvate quickly (in 1 min) and inexpensively (<$20K equipment). It has been successfully demonstrated in vivo for metabolic imaging of cancer. This technique relies on the simultaneous chemical exchange of parahydrogen, acting as a source of nuclear spin order, and [1- 13 C]pyruvate on a Ir-IMes polarization transfer catalyst at ∼0.4 μm magnetic field. The SABRE catalyst forms two kinds of complexes with parahydrogen-derived hydrides, pyruvate, and dimethyl sulfoxide, acting as a critically important coligand; however, only the complex that binds pyruvate in an equatorial position can release hyperpolarized [1- 13 C]pyruvate into the solution to enable bulk HP [1- 13 C]pyruvate production for use in molecular imaging and other applications. Here, we investigate the interplay of pH and temperature with the SABRE-SHEATH hyperpolarization of [1- 13 C]pyruvate. Temperature and pH modulate this process in remarkable and complementary ways, greatly affecting pyruvate exchange and 13 C relaxation dynamics. The overall process is optimal at pH (methanol) of 6.5–7.7 and a temperature of 6 °C: indeed, the catalyst-bound pyruvate exhibits high 13 C polarization levels in excess of 25%. The 13 C polarization results are additionally supported by 13 C relaxation dynamics at a polarization field of 0.4 microtesla. These results provide deeper understanding of the SABRE-SHEATH process and pave the way to further improve the efficiency of the hyperpolarization technique.
Authors: Isaiah Adelabu, Joseph Gyesi, Md Raduanul H. Chowdhury, Clementinah Oladun, Shiraz Nantogma, Grant Foren, Anna Samoilenko, Jessica Ettedgui, Rolf E. Swenson, Murali C. Krishna, Patrick TomHon, Thomas Theis, Henri de Maissin, Andreas B. Schmidt, Boyd M. Goodson, Sydney Scofield, Lukas Stilgenbauer, Marianna Sadagurski, Eduard Y. Chekmenev
Institutions: Wayne State University, The Barbara Ann Karmanos Cancer Institute, National Heart, Lung, and Blood Institute, National Cancer Institute, Center for Cancer Research, North Carolina State University, University of Freiburg, University Medical Center Freiburg, German Cancer Research Center, Deutsches Konsortium für Translationale Krebsforschung, Southern Illinois University Carbondale
Language: English
Subfield: Spectroscopy
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
Funders: Wayne State University, Edward Mallinckrodt, Jr. Foundation, Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, Deutschen Konsortium für Translationale Krebsforschung, National Institute on Aging, National Cancer Institute, National Institute of Environmental Health Sciences, National Institute of Biomedical Imaging and Bioengineering, Division of Chemistry
Awards: G1273940453, G136786698, G2292071163, G2321842868, G2899880, G4001306001, Rapid low-cost production of contrast agents for metabolic imaging, G583319816, G607081268, G6748151263, G868201969, G890343428, G8940636334, Plug-and-play Hyperpolarized MRI of Metabolism on Clinical Scanners, CANCER CENTER SUPPORT GRANT, Center for Leadership in Environmental Awareness and Research
OpenAlex ID: W4416542402