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Imaging of pH in vivo using hyperpolarized 13C-labelled zymonic acid

Author

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  • Stephan Düwel

    (Klinikum rechts der Isar, Technical University of Munich
    Technical University of Munich
    Institute of Medical Engineering, Technical University of Munich)

  • Christian Hundshammer

    (Klinikum rechts der Isar, Technical University of Munich
    Technical University of Munich)

  • Malte Gersch

    (Technical University of Munich
    Present address: MRC Laboratory of Molecular Biology, Francis Crick Ave, Cambridge CB2 0QH, UK)

  • Benedikt Feuerecker

    (Klinikum rechts der Isar, Technical University of Munich)

  • Katja Steiger

    (Institute of Pathology, Technical University of Munich)

  • Achim Buck

    (Research Unit Analytical Pathology, Helmholtz Zentrum München)

  • Axel Walch

    (Research Unit Analytical Pathology, Helmholtz Zentrum München)

  • Axel Haase

    (Institute of Medical Engineering, Technical University of Munich)

  • Steffen J. Glaser

    (Technical University of Munich)

  • Markus Schwaiger

    (Klinikum rechts der Isar, Technical University of Munich)

  • Franz Schilling

    (Klinikum rechts der Isar, Technical University of Munich
    Technical University of Munich
    Institute of Medical Engineering, Technical University of Munich)

Abstract

Natural pH regulatory mechanisms can be overruled during several pathologies such as cancer, inflammation and ischaemia, leading to local pH changes in the human body. Here we demonstrate that 13C-labelled zymonic acid (ZA) can be used as hyperpolarized magnetic resonance pH imaging sensor. ZA is synthesized from [1-13C]pyruvic acid and its 13C resonance frequencies shift up to 3.0 p.p.m. per pH unit in the physiological pH range. The long lifetime of the hyperpolarized signal enhancement enables monitoring of pH, independent of concentration, temperature, ionic strength and protein concentration. We show in vivo pH maps within rat kidneys and subcutaneously inoculated tumours derived from a mammary adenocarcinoma cell line and characterize ZA as non-toxic compound predominantly present in the extracellular space. We suggest that ZA represents a reliable and non-invasive extracellular imaging sensor to localize and quantify pH, with the potential to improve understanding, diagnosis and therapy of diseases characterized by aberrant acid-base balance.

Suggested Citation

  • Stephan Düwel & Christian Hundshammer & Malte Gersch & Benedikt Feuerecker & Katja Steiger & Achim Buck & Axel Walch & Axel Haase & Steffen J. Glaser & Markus Schwaiger & Franz Schilling, 2017. "Imaging of pH in vivo using hyperpolarized 13C-labelled zymonic acid," Nature Communications, Nature, vol. 8(1), pages 1-9, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15126
    DOI: 10.1038/ncomms15126
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