by Keyword: Para-hydrogen
Gierse M, Nagel L, Keim M, Lucas S, Speidel T, Lobmeyer T, Winter G, Josten F, Karaali S, Fellermann M, Scheuer J, Müller C, van Heijster F, Skinner J, Löffler J, Parker A, Handwerker J, Marshall A, Salhov A, El-Kassem B, Vassiliou C, Blanchard JW, Picazo-Frutos R, Eills J, Barth H, Jelezko F, Rasche V, Schilling F, Schwartz I, Knecht S, (2023). Parahydrogen-Polarized Fumarate for Preclinical in Vivo Metabolic Magnetic Resonance Imaging Journal Of The American Chemical Society 145, 5960-5969
We present a versatile method for the preparation of hyperpolarized [1-13C]fumarate as a contrast agent for preclinical in vivo MRI, using parahydrogen-induced polarization (PHIP). To benchmark this process, we compared a prototype PHIP polarizer to a state-of-the-art dissolution dynamic nuclear polarization (d-DNP) system. We found comparable polarization, volume, and concentration levels of the prepared solutions, while the preparation effort is significantly lower for the PHIP process, which can provide a preclinical dose every 10 min, opposed to around 90 min for d-DNP systems. With our approach, a 100 mM [1-13C]-fumarate solution of volumes up to 3 mL with 13-20% 13C-hyperpolarization after purification can be produced. The purified solution has a physiological pH, while the catalyst, the reaction side products, and the precursor material concentrations are reduced to nontoxic levels, as confirmed in a panel of cytotoxicity studies. The in vivo usage of the hyperpolarized fumarate as a perfusion agent in healthy mice and the metabolic conversion of fumarate to malate in tumor-bearing mice developing regions with necrotic cell death is demonstrated. Furthermore, we present a one-step synthesis to produce the 13C-labeled precursor for the hydrogenation reaction with high yield, starting from 13CO2 as a cost-effective source for 13C-labeled compounds.
JTD Keywords: Para-hydrogen
Van Dyke, ET, Eills, J, Picazo-Frutos, R, Sheberstov, KF, Hu, YA, Budker, D, Barskiy, DA, (2022). Relayed hyperpolarization for zero-field nuclear magnetic resonance Science Advances 8, eabp9242 
Zero- to ultralow-field nuclear magnetic resonance (ZULF NMR) is a rapidly developing form of spectroscopy that provides rich spectroscopic information in the absence of large magnetic fields. However, signal acquisition still requires a mechanism for generating a bulk magnetic moment for detection, and the currently used methods only apply to a limited pool of chemicals or come at prohibitively high cost. We demonstrate that the parahydrogen-based SABRE (signal amplification by reversible exchange)-Relay method can be used as a more general means of generating hyperpolarized analytes for ZULF NMR by observing zero-field J-spectra of [C-13]-methanol, [1-C-13]-ethanol, and [2(-13) C]-ethanol in both C-13-isotopically enriched and natural abundance samples. We explore the magnetic field dependence of the SABRE-Relay efficiency and show the existence of a second maximum at 19.0 +/- 0.3 mT. Despite presence of water, SABRE-Relay is used to hyperpolarize ethanol extracted from a store-bought sample of vodka (%P-H similar to 0.1%).
JTD Keywords: Nmr, Para-hydrogen, Sabre, Spectroscopy
