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

Stephan Düwel, Christian Hundshammer, Malte Gersch, Benedikt Feuerecker, Katja Steiger, Achim Buck, Axel Walch, Axel Haase, Steffen J. Glaser, Markus Schwaiger and Franz Schilling ()
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Stephan Düwel: Klinikum rechts der Isar, Technical University of Munich
Christian Hundshammer: Klinikum rechts der Isar, Technical University of Munich
Malte Gersch: Technical University of Munich
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

Nature Communications, 2017, vol. 8, issue 1, 1-9

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms15126

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