A Sensitive Zinc‐Activated <sup>129</sup>Xe MRI Probe

Kotera, Naoko; Tassali, Nawal; Léonce, Estelle; Boutin, Céline; Berthault, Patrick; Brotin, Thierry; Dutasta, Jean‐Pierre; Delacour, Léa; Traoré, Ténin; Buisson, David‐Alexandre; Taran, Frédéric; Coudert, Sylvie; Rousseau, Bernard

doi:10.1002/anie.201109194

Cited by 76 publications

(55 citation statements)

References 38 publications

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“…40 In one proof-of-concept experiment, Berthault et al . decorated cryptophane with six carboxylic acids to create a pH sensor: unique chemical shifts were measured over the pH 3.5-5.5 range with a total Δδ of 3.55 ppm.…”

Section: Introductionmentioning

confidence: 99%

A “Smart” ¹²⁹Xe NMR Biosensor for pH-Dependent Cell Labeling

2015

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Here we present a “smart” xenon-129 NMR biosensor that undergoes a peptide conformational change and labels cancer cells at acidic pH. To a cryptophane host molecule with high Xe affinity, we conjugated a 30mer EALA-repeat peptide that is alpha-helical at pH 5.5 and disordered at pH 7.5. The 129Xe NMR chemical shift at rt was strongly pH-dependent (Δδ = 3.4 ppm): δ = 64.2 ppm at pH 7.5 vs. δ = 67.6 ppm at pH 5.5 where Trp(peptide)-cryptophane interactions were evidenced by Trp fluorescence quenching. Using Hyper-CEST NMR, we probed peptido-cryptophane detection limits at low-picomolar (10−11 M) concentration, which compares favourably to other NMR pH sensors at 10−2−10−3 M. Finally, in biosensor-HeLa cell solutions, peptide-cell membrane insertion at pH 5.5 generated a 13.4 ppm downfield cryptophane-129Xe NMR chemical shift relative to pH 7.5 studies. This highlights new uses for 129Xe as an ultrasensitive probe of peptide structure and function, along with potential applications for pH-dependent cell labeling in cancer diagnosis and treatment.

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Section: Introductionmentioning

confidence: 99%

A “Smart” ¹²⁹Xe NMR Biosensor for pH-Dependent Cell Labeling

2015

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“…In the direct detection methods, fast repetition of spectrallyselective pulses around the small reservoir resonance frequency (and detection after each pulse) uses the chemical exchange between the two environments to gradually increase the signal-to-noise ratio. 56,57 The repetition rhythm is chosen according to the exchange rate of xenon between the two environments.…”

Section: Methodsmentioning

confidence: 99%

¹²⁹Xe NMR-based sensors: biological applications and recent methods

Mari

Berthault

2017

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aXenon is a first-rate sensor of biological events, due to its large polarizable electron cloud inducing significant modification of NMR parameters through slight changes in its local environment. The use of xenon as a sensor is of increasing interest for sensitive magnetic resonance imaging, since its signal can be enhanced by several orders of magnitude, mainly by spinexchange optical pumping. Furthermore xenon can be vectorized toward targets of interest by using functionalized host systems, enabling their detection at subnanomolar concentrations. Associated with a new generation of detection methods this gives rise to a powerful molecular imaging approach, where xenon can be delivered on purpose several times after introduction of the functionalized host system. IntroductionFrom simple photograph of the inside of the human body providing information on bone structure or form and abnormalities of various organs, molecular imaging now offers a dynamic view of biological processes occurring locally, witnessing for instance the presence of infectious cells or metabolic deregulations. The development of powerful imaging techniques is the key to early diagnosis of disease, best follow-up treatments and also biomedical research tools. These techniques developed particularly in the 21th century form part of the molecular imaging concept. Magnetic resonance imaging (MRI) is a good compromise to achieve molecular imaging in vivo in real time without any perturbative radiation. The major advantages of MRI are its potential high spatial resolution (25-100 µm), its low invasiveness, its harmlessness and the excellent tissue contrast it can provide. In this context, MRI complements and sometimes overruns other molecular imaging approaches by enabling monitoring of events at the cellular or even subcellular level. However, classical implementation of this technique suffers from low sensitivity due to the very low population differences between nuclear spin energy levels at Boltzmann equilibrium. Hyperpolarization techniques 1 that transiently increase the nuclear spin polarization of a very dilute agent by several orders of magnitude circumvent the MRI sensitivity problem. Among the species that can be spinhyperpolarized, xenon is of high interest, due to its exogenous nature (leading to the absence of background signal) and the fact that it can act as a spy of biological events without interfering with them. Moreover, it can be endlessly reloaded and simply removed from the sample since it is a gas at ambient temperature and pressure. Finally, owing to the high deformability of its large electron cloud xenon is deeply sensitive to its local environment and constitutes a perfect probe for various biological interactions. Soluble in most biological fluids, xenon can cross the plasma membrane in a few tens of milliseconds without losing its hyperpolarization. 2The initial applications of hyperpolarized xenon in biology were the anatomical imaging of the lung 3 and the investigation of hydrophobic binding pockets in proteins ...

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“…To date, cryptophane-based sensors that use specific binding to the target have been implemented for sensing the enzyme MMP7, [143] nucleotides, [144] human carbonic anhydrase, [145] MHC class II, [146] zinc ions, [147] the glycoprotein CD14 [148] and the receptors for integrin, [149] transferrin, [150] EGF, [151] and folate. [152] An indirect binding approach was pursued through in situ click chemistry with metabolically labeled cell surface glycans.…”

Section: 129xe Cages and Hyper-cest Mrimentioning

confidence: 99%

NMR Hyperpolarization Techniques of Gases

Barskiy

Coffey

Nikolaou

et al. 2016

Chemistry A European J

153

117

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Nuclear spin polarization can be significantly increased through the process of hyperpolarization, leading to an increase in the sensitivity of nuclear magnetic resonance (NMR) experiments by 4–8 orders of magnitude. Hyperpolarized gases, unlike liquids and solids, can be more readily separated and purified from the compounds used to mediate the hyperpolarization processes. These pure hyperpolarized gases enabled many novel MRI applications including the visualization of void spaces, imaging of lung function, and remote detection. Additionally, hyperpolarized gases can be dissolved in liquids and can be used as sensitive molecular probes and reporters. This mini-review covers the fundamentals of the preparation of hyperpolarized gases and focuses on selected applications of interest to biomedicine and materials science.

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A Sensitive Zinc‐Activated ¹²⁹Xe MRI Probe

Cited by 76 publications

References 38 publications

A “Smart” ¹²⁹Xe NMR Biosensor for pH-Dependent Cell Labeling

A “Smart” ¹²⁹Xe NMR Biosensor for pH-Dependent Cell Labeling

¹²⁹Xe NMR-based sensors: biological applications and recent methods

NMR Hyperpolarization Techniques of Gases

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A Sensitive Zinc‐Activated 129Xe MRI Probe

Cited by 76 publications

References 38 publications

A “Smart” 129Xe NMR Biosensor for pH-Dependent Cell Labeling

A “Smart” 129Xe NMR Biosensor for pH-Dependent Cell Labeling

129Xe NMR-based sensors: biological applications and recent methods

NMR Hyperpolarization Techniques of Gases

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Product

Resources

About

A Sensitive Zinc‐Activated ¹²⁹Xe MRI Probe

A “Smart” ¹²⁹Xe NMR Biosensor for pH-Dependent Cell Labeling

A “Smart” ¹²⁹Xe NMR Biosensor for pH-Dependent Cell Labeling

¹²⁹Xe NMR-based sensors: biological applications and recent methods