Amino Acid-Derived Sensors for Specific Zn2+ Detection Using Hyperpolarized 13 C Magnetic Resonance Spectroscopy - PubMed (original) (raw)

. 2019 Sep 12;25(51):11842-11846.

doi: 10.1002/chem.201902771. Epub 2019 Aug 20.

David E Korenchan 1, Paola M Perez 1, Céline Taglang 1, Thomas R Hayes 1, Renuka Sriram 1, Robert Bok 1, Andrew S Hong 1, Yunkou Wu 2, Henry Li 1, Zhen Wang 1, John Kurhanewicz 1 3, David M Wilson 1, Robert R Flavell 1 3

Affiliations

Amino Acid-Derived Sensors for Specific Zn2+ Detection Using Hyperpolarized 13 C Magnetic Resonance Spectroscopy

Sinan Wang et al. Chemistry. 2019.

Abstract

Alterations in Zn2+ concentration are seen in normal tissues and in disease states, and for this reason imaging of Zn2+ is an area of active investigation. Herein, enriched [1-13 C]cysteine and [1-13 C2 ]iminodiacetic acid were developed as Zn2+ -specific imaging probes using hyperpolarized 13 C magnetic resonance spectroscopy. [1-13 C]cysteine was used to accurately quantify Zn2+ in complex biological mixtures. These sensors can be employed to detect Zn2+ via imaging mechanisms including changes in 13 C chemical shift, resonance linewidth, or T1 .

Keywords: chemical shifts; hyperpolarization; imaging agents; magnetic resonance imaging; zinc.

© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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Figures

Figure 1.

Figure 1.

Approach to specific detection of Zn2+ via hyperpolarized magnetic resonance spectroscopy (A) Structures of [1-13C]Cys and [1-13C2]IDA. (B) Specificity of 50 mM [1-13C]Cys and [1-13C2]IDA for physiological cations (present at 1 equivalent). pH-dependence of chemical shift was measured at pH 7.4 and 6.5, the physiologically relevant extracellular range.

Figure 2.

Figure 2.

Response of [1-13C]Cys and [1-13C2]IDA to Zn2+ can be detected by several magnetic resonance mechanisms. (A) 13C NMR Spectra for 50 mM [1-13C]Cys with varying Zn2+ concentrations (B) Standard titration curve of [1-13C]Cys in response to various Zn2+ concentrations. The insert shows the titration curve at low Zn2+ equivalents. (C) Spectra for 50 mM [1-13C2]IDA with various Zn2+ concentrations highlighting formation of a Zn2+ bound species, and increased linewidth upon Zn2+ binding. * represents natural abundance citric acid peak (D) Standard titration curve of [1-13C2]IDA.

Figure 3.

Figure 3.

Dynamic 13C NMR spectra following polarization of [1-13C]Cys (left) and [1-13C2]IDA (right). Pulse conditions were TR = 3s, 5º hard pulses, 10 kHz spectral width, 30 timepoints, nominal spectral resolution = 0.5 Hz.

Figure 4.

Figure 4.

HP [1-13C]Cys accurately quantifies Zn2+ concentration in phantom imaging experiments through use of chemical shift measurements. (A) Phantom imaging conducted using 40 mM [1-13C]Cys. (B) Phantom experiment conducted using 4 mM [1-13C]Cys, indicating high sensitivity for low concentrations of Zn2+.

Figure 5.

Figure 5.

Hyperpolarized [1-13C]Cys phantom imaging experiment demonstrating accurate Zn2+ quantification in biological samples. Accurate detection of Zn2+ concentration in presence of exogenous Zn2+ and in the presence of Zn2+-chelating TPA demonstrates specificity of the probe for Zn2+ over other endogenous analytes.

Scheme 1.

Scheme 1.

Synthesis of [1-13C2]IDA disodium salt.

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