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by Keyword: Carbon-13
Gross, Philipp R, Petersen, Stefan, Wang, Zirun, Shamshiri, Behnam, de Maissin, Henri, Lucas, Sebastian, Gorka, Oliver, Hess, Lisa, Marco-Rius, Irene, Mangas-Florencio, Lluis, Martins, Andre F, Boehm-Sturm, Philipp, Zaitsev, Maxim, Zeiser, Robert, Hovener, Jan-Bernd, Reinheckel, Thomas, Gross, Olaf, Schmidt, Andreas B, (2026). Minute-Scale Repeated Metabolic Probing of Living Cells Enabled by Rapid Parahydrogen-Based Hyperpolarization ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 65, e4855536
Hyperpolarized (HP) 13C nuclear magnetic resonance (NMR) spectroscopy enables real-time observation of metabolic fluxes but is typically limited to single-shot measurements due to complex preparation procedures and low experimental throughput. Here, we established a rapid and experimentally accessible workflow for temporally controlled HP measurements in living cells. Using SABRE-SHEATH at 0.4 & micro;T, we achieved 7.7% +/- 0.2% 13C polarization of 50 mM [1-13C]pyruvate within 60 s. Simple 1:50 dilution with phosphate-buffered D2O yielded cell-compatible solutions that retained 5.3% +/- 0.4% polarization of 1.3 mM pyruvate without multi-step purification. Combined with a simplified agarose bead immobilization approach, this enabled four injections of HP pyruvate into the same HeLa cell population within 7 min. Under rapid (approximate to 2 min) reinjection intervals, the pyruvate-to-lactate conversion progressively declined, whereas stable metabolic conversion was maintained at 20 min intervals with intermittent cell medium perfusion. These findings demonstrate that rapid repeated substrate delivery can transiently exhaust cellular metabolic conversion capacity. This experimentally accessible operating mode enables the study of short-term metabolic dynamics that remain obscured in conventional single-shot HP-NMR or long timescale thermally polarized NMR measurements.
JTD Keywords: Bioreactor, Carbon-13, Culture, Glucose, Hyperpolarization, Metabolism, Para-hydrogen, Parahydrogen, Polarization, Pyruvate, Sabre
Schmidt, AB, Eills, J, Dagys, L, Gierse, M, Bock, M, Lucas, S, Bock, M, Schwartz, I, Zaitsev, M, Chekmenev, EY, Knecht, S, (2023). Over 20% Carbon-13 Polarization of Perdeuterated Pyruvate Using Reversible Exchange with Parahydrogen and Spin-Lock Induced Crossing at 50 μT Journal of Physical Chemistry Letters 14, 5305-5309
Carbon-13 hyperpolarized pyruvate is about to become the next-generation contrast agent for molecular magnetic resonance imaging of cancer and other diseases. Here, efficient and rapid pyruvate hyperpolarization is achieved via signal amplification by reversible exchange (SABRE) with parahydrogen through synergistic use of substrate deuteration, alternating, and static microtesla magnetic fields. Up to 22 and 6% long-lasting 13C polarization (T1 = 3.7 ± 0.25 and 1.7 ± 0.1 min) is demonstrated for the C1 and C2 nuclear sites, respectively. The remarkable polarization levels become possible as a result of favorable relaxation dynamics at the microtesla fields. The ultralong polarization lifetimes will be conducive to yielding high polarization after purification, quality assurance, and injection of the hyperpolarized molecular imaging probes. These results pave the way to future in vivo translation of carbon-13 hyperpolarized molecular imaging probes prepared by this approach.
JTD Keywords: hydrogen, nmr, Carbon isotopes, Carbon-13, Magnetic resonance imaging, Magnetic resonance spectroscopy, Pyruvic acid, Sabre