Hyperpolarized Amino Acid Derivatives as Multivalent Magnetic Resonance pH Sensor Molecules
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. Howev...
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doaj-9dc185ca9b6f48768de81477f55d125e2020-11-25T00:55:45ZengMDPI AGSensors1424-82202018-02-0118260010.3390/s18020600s18020600Hyperpolarized Amino Acid Derivatives as Multivalent Magnetic Resonance pH Sensor MoleculesChristian Hundshammer0Stephan Düwel1David Ruseckas2Geoffrey Topping3Piotr Dzien4Christoph Müller5Benedikt Feuerecker6Jan B. Hövener7Axel Haase8Markus Schwaiger9Steffen J. Glaser10Franz Schilling11Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, 81675 München, GermanyDepartment of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, 81675 München, GermanyDepartment of Chemistry, Technical University of Munich, 85748 Garching, GermanyDepartment of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, 81675 München, GermanyDepartment of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, 81675 München, GermanyDepartment of Radiology, Medical Physics, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyDepartment of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, 81675 München, GermanySection for Biomedical Imaging, Molecular Imaging North Competence Center (MOINCC), Department for Radiology and Neuroradiology, University Medical Center Kiel, University Kiel, 24118 Kiel, GermanyMunich School of Bioengineering, Technical University of Munich, 85748 Garching, GermanyDepartment of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, 81675 München, GermanyDepartment of Chemistry, Technical University of Munich, 85748 Garching, GermanyDepartment of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, 81675 München, GermanypH 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.http://www.mdpi.com/1424-8220/18/2/600pH sensorshyperpolarizeddissolution dynamic nuclear polarizationmagnetic resonance spectroscopic imagingnuclear magnetic resonanceamino acids |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Christian Hundshammer Stephan Düwel David Ruseckas Geoffrey Topping Piotr Dzien Christoph Müller Benedikt Feuerecker Jan B. Hövener Axel Haase Markus Schwaiger Steffen J. Glaser Franz Schilling |
spellingShingle |
Christian Hundshammer Stephan Düwel David Ruseckas Geoffrey Topping Piotr Dzien Christoph Müller Benedikt Feuerecker Jan B. Hövener Axel Haase Markus Schwaiger Steffen J. Glaser Franz Schilling Hyperpolarized Amino Acid Derivatives as Multivalent Magnetic Resonance pH Sensor Molecules Sensors pH sensors hyperpolarized dissolution dynamic nuclear polarization magnetic resonance spectroscopic imaging nuclear magnetic resonance amino acids |
author_facet |
Christian Hundshammer Stephan Düwel David Ruseckas Geoffrey Topping Piotr Dzien Christoph Müller Benedikt Feuerecker Jan B. Hövener Axel Haase Markus Schwaiger Steffen J. Glaser Franz Schilling |
author_sort |
Christian Hundshammer |
title |
Hyperpolarized Amino Acid Derivatives as Multivalent Magnetic Resonance pH Sensor Molecules |
title_short |
Hyperpolarized Amino Acid Derivatives as Multivalent Magnetic Resonance pH Sensor Molecules |
title_full |
Hyperpolarized Amino Acid Derivatives as Multivalent Magnetic Resonance pH Sensor Molecules |
title_fullStr |
Hyperpolarized Amino Acid Derivatives as Multivalent Magnetic Resonance pH Sensor Molecules |
title_full_unstemmed |
Hyperpolarized Amino Acid Derivatives as Multivalent Magnetic Resonance pH Sensor Molecules |
title_sort |
hyperpolarized amino acid derivatives as multivalent magnetic resonance ph sensor molecules |
publisher |
MDPI AG |
series |
Sensors |
issn |
1424-8220 |
publishDate |
2018-02-01 |
description |
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. |
topic |
pH sensors hyperpolarized dissolution dynamic nuclear polarization magnetic resonance spectroscopic imaging nuclear magnetic resonance amino acids |
url |
http://www.mdpi.com/1424-8220/18/2/600 |
work_keys_str_mv |
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