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Abstract #5080

In Vivo Imaging of Tumor Metabolic Heterogeneity Using [1-13C]Pyruvate-d3 Hyperpolarized By Reversible Exchange With Parahydrogen

Stefan Petersen1, Philipp Groß1,2, Luca Nagel3, Robert Willing1,2, Lisa Heß4, Julia Mitschke4, Nicole Klemm4, Christoph A. Müller5, Stephan Knecht5, Moritz Weigt1, Michael Bock1, Dominik von Elverfeldt1, Maxim Zaitsev1, Eduard Y. Chekmenev6, Jan-Bernd Hövener7, André F. Martins8,9, Franz Schilling3,10, Thomas Reinheckel2,4, and Andreas B. Schmidt1,2,6
1Division of Medical Physics, Department of Diagnostic and Interventional Radiology, Faculty of Medicine, University of Freiburg, University Medical Center Freiburg, Freiburg 79106, Germany, 2German Cancer Consortium (DKTK), partner site Freiburg, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany, 3Department of Nuclear Medicine, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich 81675, Germany, 4Institute of Molecular Medicine and Cell Research, Faculty of Medicine, University of Freiburg, Freiburg 79104, Germany, 5NVision Imaging Technologies GmbH, Ulm 89081, Germany, 6Department of Chemistry, Integrative Biosciences (Ibio), Karmanos Cancer Institute (KCI), Wayne State University, Detroit 48202, MI, United States, 7Sektion Biomedizinsche Bildgebung, Molecular Imaging North Competence Center MOINCC, Klinik für Radiologie und Neuroradiologie, University Hospital Schleswig-Holstein, Kiel University, Kiel, Germany, 8Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen 72076, Germany, 9German Cancer Consortium (DKTK), partner site Tübingen, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany, 10German Cancer Consortium (DKTK), partner site Munich, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany

Synopsis

Keywords: Hyperpolarized MR (Non-Gas), Contrast Agent

Motivation: Hyperpolarized [1-13C]pyruvate MRI is promising for studying cancer metabolism and assessing early therapy response but requires high-throughput and less complex hyperpolarization techniques for wide availability.

Goal(s): Demonstrating metabolic imaging in a genetic mouse model of metastasizing breast cancer (MMTV-PyMT) using purified [1-13C]-pyruvate-d3 hyperpolarized via parahydrogen-based Signal Amplification By Reversible Exchange (SABRE).

Approach: Our rapid (6 min) and efficient hyperpolarization method yielded highly-polarized (>10%) [1-13C]-pyruvate-d3 in safe aqueous solutions.

Results: Administered to two PyMT-mice, 13C chemical shift imaging detected the injected pyruvate and metabolized [1-13C]-lactate. Analysis revealed elevated lactate levels in tumors compared to healthy breast tissue, highlighting tumor compartments with distinct metabolic profiles.

Impact: We showcase our rapid, cost-effective SABRE hyperpolarization approach, yielding safe, highly-polarized pyruvate for inaugural cancer metabolic investigations. This innovation expands high-throughput preclinical HP-MRI research, enabling comprehensive exploration of tumor biology, metabolic processes, and therapeutic responses in cancer.

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Abstract

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