In Vivo Metabolic Imaging of [1‐13C]Pyruvate‐d3 Hyperpolarized By Reversible Exchange With Parahydrogen**

Author:

de Maissin Henri12ORCID,Groß Philipp R.1ORCID,Mohiuddin Obaid1,Weigt Moritz1ORCID,Nagel Luca3ORCID,Herzog Marvin1,Wang Zirun1,Willing Robert12ORCID,Reichardt Wilfried1ORCID,Pichotka Martin1,Heß Lisa4,Reinheckel Thomas24ORCID,Jessen Henning J.5ORCID,Zeiser Robert26ORCID,Bock Michael1ORCID,von Elverfeldt Dominik1ORCID,Zaitsev Maxim1ORCID,Korchak Sergey78,Glöggler Stefan78,Hövener Jan‐Bernd9ORCID,Chekmenev Eduard Y.10ORCID,Schilling Franz311ORCID,Knecht Stephan12,Schmidt Andreas B.1210ORCID

Affiliation:

1. Division of Medical Physics, Department of Radiology Medical Center Faculty of Medicine University of Freiburg Killianstr. 5a 79106 Freiburg Germany

2. German Cancer Consortium (DKTK) partner site Freiburg and German Cancer Research Center (DKFZ) Im Neuenheimer Feld 280 69120 Heidelberg Germany

3. Department of Nuclear Medicine Klinikum rechts der Isar Technical University of Munich Ismaninger Str. 22 81675 Munich Germany

4. Institute of Molecular Medicine and Cell Research Faculty of Medicine University of Freiburg Stefan-Meier-Str. 17 79104 Freiburg Germany

5. Bioorganic Chemistry Institute of Organic Chemistry Albert-Ludwigs-University of Freiburg Albertstrasse 21 79104 Freiburg Germany

6. Hematology and Oncology Department of Medicine I Medical Center Faculty of Medicine University of Freiburg Hugstetter Strasse 55 79106 Freiburg Germany

7. NMR Signal Enhancement Group Max Planck Institute for Multidisciplinary Sciences Am Fassberg 11 37077 Göttingen Germany

8. Center for Biostructural Imaging of Neurodegeneration of the University Medical Center Göttingen Von-Siebold-Str. 3 A 37075 Göttigen Germany

9. Section Biomedical Imaging SBMI Molecular Imaging North Competence Center MOINCC Department of Radiology and Neuroradiology University Hospital Schleswig-Holstein Kiel University 24105 Kiel Germany

10. Department of Chemistry Integrative Biosciences (Ibio) Karmanos CancerInstitute (KCI) Wayne State University Detroit MI 48202 USA

11. German Cancer Consortium (DKTK) partner site Munich and German Cancer Research Center (DKFZ) Im Neuenheimer Feld 280 69120 Heidelberg Germany

12. NVision Imaging Technologies GmbH 89081 Ulm Germany

Abstract

AbstractMetabolic magnetic resonance imaging (MRI) using hyperpolarized (HP) pyruvate is becoming a non‐invasive technique for diagnosing, staging, and monitoring response to treatment in cancer and other diseases. The clinically established method for producing HP pyruvate, dissolution dynamic nuclear polarization, however, is rather complex and slow. Signal Amplification By Reversible Exchange (SABRE) is an ultra‐fast and low‐cost method based on fast chemical exchange. Here, for the first time, we demonstrate not only in vivo utility, but also metabolic MRI with SABRE. We present a novel routine to produce aqueous HP [1‐13C]pyruvate‐d3 for injection in 6 minutes. The injected solution was sterile, non‐toxic, pH neutral and contained ≈30 mM [1‐13C]pyruvate‐d3 polarized to ≈11 % (residual 250 mM methanol and 20 μM catalyst). It was obtained by rapid solvent evaporation and metal filtering, which we detail in this manuscript. This achievement makes HP pyruvate MRI available to a wide biomedical community for fast metabolic imaging of living organisms.

Funder

Bundesministerium für Bildung und Forschung

Deutschen Konsortium für Translationale Krebsforschung

Deutsche Forschungsgemeinschaft

HORIZON EUROPE European Research Council

Medizinische Fakultät der Albert-Ludwigs-Universität Freiburg

Wayne State University

National Science Foundation

Publisher

Wiley

Subject

General Chemistry,Catalysis

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