Deuteration of Hyperpolarized13C-Labeled Zymonic Acid Enables Sensitivity-Enhanced Dynamic MRI of pH
| Autor: | Steffen J. Glaser, Christian Hundshammer, Benedikt Feuerecker, Franz Schilling, Malte Gersch, Christoph Scheurer, Simone Swantje Köcher, Markus Schwaiger, Axel Haase, Stephan Düwel |
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| Rok vydání: | 2017 |
| Předmět: |
Chemistry
Spatially resolved Hyperpolarized 13c Spin–lattice relaxation 010402 general chemistry 01 natural sciences Response to treatment Atomic and Molecular Physics and Optics 030218 nuclear medicine & medical imaging 0104 chemical sciences 03 medical and health sciences 0302 clinical medicine Nuclear magnetic resonance Dynamic contrast-enhanced MRI Extracellular Hyperpolarization (physics) Physical and Theoretical Chemistry Biosensor |
| Zdroj: | ChemPhysChem. 18:2422-2425 |
| ISSN: | 1439-4235 |
| DOI: | 10.1002/cphc.201700779 |
| Popis: | Aberrant pH is characteristic of many pathologies such as ischemia, inflammation or cancer. Therefore, a non-invasive and spatially resolved pH determination is valuable for disease diagnosis, characterization of response to treatment and the design of pH-sensitive drug-delivery systems. We recently introduced hyperpolarized [1,5-13C2]zymonic acid (ZA) as a novel MRI probe of extracellular pH utilizing dissolution dynamic polarization (DNP) for a more than 10000-fold signal enhancement of the MRI signal. Here we present a strategy to enhance the sensitivity of this approach by deuteration of ZA yielding [1,5-13C2, 3,6,6,6-D4]zymonic acid (ZAd), which prolongs the liquid state spin lattice relaxation time (T1) by up to 39 % in vitro. Measurements with ZA and ZAd on subcutaneous MAT B III adenocarcinoma in rats show that deuteration increases the signal-to-noise ratio (SNR) by up to 46 % in vivo. Furthermore, we demonstrate a proof of concept for real-time imaging of dynamic pH changes in vitro using ZAd, potentially allowing for the characterization of rapid acidification/basification processes in vivo. |
| Databáze: | OpenAIRE |
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