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Sensors 2018, 18(2), 600; https://doi.org/10.3390/s18020600

Hyperpolarized Amino Acid Derivatives as Multivalent Magnetic Resonance pH Sensor Molecules

1
Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, 81675 München, Germany
2
Department of Chemistry, Technical University of Munich, 85748 Garching, Germany
3
Munich School of Bioengineering, Technical University of Munich, 85748 Garching, Germany
4
Department of Radiology, Medical Physics, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
5
German Consortium for Cancer Research (DKTK), 69120 Heidelberg, Germany
6
German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
7
Section for Biomedical Imaging, Molecular Imaging North Competence Center (MOINCC), Department for Radiology and Neuroradiology, University Medical Center Kiel, University Kiel, 24118 Kiel, Germany
*
Author to whom correspondence should be addressed.
Received: 9 January 2018 / Revised: 7 February 2018 / Accepted: 8 February 2018 / Published: 15 February 2018
(This article belongs to the Special Issue Biosensors for Theranostics)
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Abstract

pH is a tightly regulated physiological parameter that is often altered in diseased states like cancer. The development of biosensors that can be used to non-invasively image pH with hyperpolarized (HP) magnetic resonance spectroscopic imaging has therefore recently gained tremendous interest. However, most of the known HP-sensors have only individually and not comprehensively been analyzed for their biocompatibility, their pH sensitivity under physiological conditions, and the effects of chemical derivatization on their logarithmic acid dissociation constant (pKa). Proteinogenic amino acids are biocompatible, can be hyperpolarized and have at least two pH sensitive moieties. However, they do not exhibit a pH sensitivity in the physiologically relevant pH range. Here, we developed a systematic approach to tailor the pKa of molecules using modifications of carbon chain length and derivatization rendering these molecules interesting for pH biosensing. Notably, we identified several derivatives such as [1-13C]serine amide and [1-13C]-2,3-diaminopropionic acid as novel pH sensors. They bear several spin-1/2 nuclei (13C, 15N, 31P) with high sensitivity up to 4.8 ppm/pH and we show that 13C spins can be hyperpolarized with dissolution dynamic polarization (DNP). Our findings elucidate the molecular mechanisms of chemical shift pH sensors that might help to design tailored probes for specific pH in vivo imaging applications. View Full-Text
Keywords: pH sensors; hyperpolarized; dissolution dynamic nuclear polarization; magnetic resonance spectroscopic imaging; nuclear magnetic resonance; amino acids pH sensors; hyperpolarized; dissolution dynamic nuclear polarization; magnetic resonance spectroscopic imaging; nuclear magnetic resonance; amino acids
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Hundshammer, C.; Düwel, S.; Ruseckas, D.; Topping, G.; Dzien, P.; Müller, C.; Feuerecker, B.; Hövener, J.B.; Haase, A.; Schwaiger, M.; Glaser, S.J.; Schilling, F. Hyperpolarized Amino Acid Derivatives as Multivalent Magnetic Resonance pH Sensor Molecules. Sensors 2018, 18, 600.

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