Parahydrogen-Polarized Fumarate for Preclinical in Vivo Metabolic Magnetic Resonance Imaging.

Autor:	Gierse M; NVision Imaging Technologies GmbH, 89081 Ulm, Germany.; Institute for Quantum Optics (IQO) and Center for Integrated Quantum Science and Technology (IQST), Ulm University, 89081 Ulm, Germany., Nagel L; Department of Nuclear Medicine, TUM School of Medicine, Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany., Keim M; NVision Imaging Technologies GmbH, 89081 Ulm, Germany., Lucas S; NVision Imaging Technologies GmbH, 89081 Ulm, Germany., Speidel T; Core Facility Small Animal MRI, Medical Faculty, Ulm University, 89081 Ulm, Germany., Lobmeyer T; Core Facility Small Animal MRI, Medical Faculty, Ulm University, 89081 Ulm, Germany., Winter G; Department of Nuclear Medicine, Ulm University, 89081 Ulm, Germany., Josten F; NVision Imaging Technologies GmbH, 89081 Ulm, Germany., Karaali S; NVision Imaging Technologies GmbH, 89081 Ulm, Germany., Fellermann M; Institute of Experimental and Clinical Pharmacology, Toxicology and Pharmacology of Natural Products, University of Ulm Medical Center, 89081 Ulm, Germany., Scheuer J; NVision Imaging Technologies GmbH, 89081 Ulm, Germany., Müller C; NVision Imaging Technologies GmbH, 89081 Ulm, Germany., van Heijster F; Department of Nuclear Medicine, TUM School of Medicine, Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany., Skinner J; Department of Nuclear Medicine, TUM School of Medicine, Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany., Löffler J; Department of Nuclear Medicine, Ulm University, 89081 Ulm, Germany., Parker A; NVision Imaging Technologies GmbH, 89081 Ulm, Germany., Handwerker J; NVision Imaging Technologies GmbH, 89081 Ulm, Germany., Marshall A; NVision Imaging Technologies GmbH, 89081 Ulm, Germany.; Institute for Quantum Optics (IQO) and Center for Integrated Quantum Science and Technology (IQST), Ulm University, 89081 Ulm, Germany., Salhov A; NVision Imaging Technologies GmbH, 89081 Ulm, Germany.; Racah Institute of Physics, The Hebrew University of Jerusalem, Jerusalem, 91904, Givat Ram, Israel., El-Kassem B; NVision Imaging Technologies GmbH, 89081 Ulm, Germany., Vassiliou C; NVision Imaging Technologies GmbH, 89081 Ulm, Germany., Blanchard JW; NVision Imaging Technologies GmbH, 89081 Ulm, Germany., Picazo-Frutos R; Helmholtz-Institut Mainz, GSI Helmholtzzentrum für Schwerionenforschung, Mainz 55128, Germany.; Johannes Gutenberg-Universität Mainz, Mainz 55128, Germany., Eills J; Institute for Bioengineering of Catalonia, 08028 Barcelona, Spain., Barth H; Institute of Experimental and Clinical Pharmacology, Toxicology and Pharmacology of Natural Products, University of Ulm Medical Center, 89081 Ulm, Germany., Jelezko F; NVision Imaging Technologies GmbH, 89081 Ulm, Germany.; Institute for Quantum Optics (IQO) and Center for Integrated Quantum Science and Technology (IQST), Ulm University, 89081 Ulm, Germany., Rasche V; Core Facility Small Animal MRI, Medical Faculty, Ulm University, 89081 Ulm, Germany., Schilling F; Department of Nuclear Medicine, TUM School of Medicine, Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany., Schwartz I; NVision Imaging Technologies GmbH, 89081 Ulm, Germany., Knecht S; NVision Imaging Technologies GmbH, 89081 Ulm, Germany.
Jazyk:	angličtina
Zdroj:	Journal of the American Chemical Society [J Am Chem Soc] 2023 Mar 15; Vol. 145 (10), pp. 5960-5969. Date of Electronic Publication: 2023 Mar 01.
DOI:	10.1021/jacs.2c13830
Abstrakt:	We present a versatile method for the preparation of hyperpolarized [1- 13 C]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- 13 C]-fumarate solution of volumes up to 3 mL with 13-20% 13 C-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 13 C-labeled precursor for the hydrogenation reaction with high yield, starting from 13 CO 2 as a cost-effective source for 13 C-labeled compounds.
Databáze:	MEDLINE
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