Optimization of SABRE for polarization of the tuberculosis drugs pyrazinamide and isoniazid

Zeng, Haifeng; Xu, Jiadi; Gillen, Joseph; McMahon, Michael T.; Artemov, Dmitri; Tyburn, Jean Max; Lohman, Joost A. B.; Mewis, Ryan E.; Atkinson, Kevin D.; Green, Gary; Duckett, Simon B.; Zijl, Peter van

doi:10.1016/j.jmr.2013.09.012

Cited by 125 publications

(109 citation statements)

References 29 publications

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“…[7a] Relatively low concentrations of HP compounds such as Py are sufficient for low-field molecular MRI. SABRE already offers a range of substrates that can be hyperpolarized, including biocompatible molecules and metabolites, [25] and the list is likely to expand. Whereas the initially demonstrated signal enhancements with heterogeneous SABRE [13] and SABRE in water [14a, c] were relatively low, they can potentially enable SABRE imaging and spectroscopy in vivo.…”

Section: Resultsmentioning

confidence: 99%

In Situ and Ex Situ Low‐Field NMR Spectroscopy and MRI Endowed by SABRE Hyperpolarization

et al. 2014

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By using 5.75 and 47.5 mT nuclear magnetic resonance (NMR) spectroscopy, up to 105-fold sensitivity enhancement through signal amplification by reversible exchange (SABRE) was enabled, and subsecond temporal resolution was used to monitor an exchange reaction that resulted in the buildup and decay of hyperpolarized species after parahydrogen bubbling. We demonstrated the high-resolution low-field proton magnetic resonance imaging (MRI) of pyridine in a 47.5 mT magnetic field endowed by SABRE. Molecular imaging (i.e. imaging of dilute hyperpolarized substances rather than the bulk medium) was conducted in two regimes: in situ real-time MRI of the reaction mixture (in which pyridine was hyperpolarized), and ex situ MRI (in which hyperpolarization decays) of the liquid hyperpolarized product. Low-field (milli-Tesla range, e.g. 5.75 and 47.5 mT used in this study) parahydrogen-enhanced NMR and MRI, which are free from the limitations of high-field magnetic resonance (including susceptibility-induced gradients of the static magnetic field at phase interfaces), potentially enables new imaging applications as well as differentiation of hyperpolarized chemical species on demand by exploiting spin manipulations with static and alternating magnetic fields.

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Section: Resultsmentioning

confidence: 99%

In Situ and Ex Situ Low‐Field NMR Spectroscopy and MRI Endowed by SABRE Hyperpolarization

et al. 2014

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“…With this approach, parahydrogen protons are not added to the substrate but the hyperpolarization transfer takes place on a transient adduct formed by the substrate, parahydrogen and the organometallic complex. This method has been successfully tested on several biologically relevant molecules such as pyrimidines, purines, amino acids and drugs 24,25 . However, in vivo application still suffers from low polarization levels and the need for suitable organometallic complex to efficiently renew hyperpolarization 26 .…”

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ParaHydrogen Induced Polarization of 13C carboxylate resonance in acetate and pyruvate

2015

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The advent of nuclear spins hyperpolarization techniques represents a breakthrough in the field of medical diagnoses by magnetic resonance imaging. Dynamic nuclear polarization (DNP) is the most widely used method, and hyperpolarized metabolites such as [1-13 C]-pyruvate are shown to report on status of tumours. Parahydrogen-induced polarization (PHIP) is a chemistry-based technique, easier to handle and much less expensive in respect to DNP, with significantly shorter polarization times. Its main limitation is the availability of unsaturated precursors for the target substrates; for instance, acetate and pyruvate cannot be obtained by direct incorporation of the parahydrogen molecule. Herein we report a method that allows us to achieve hyperpolarization in this kind of molecule by means of a tailored precursor containing a hydrogenable functionality that, after polarization transfer to the target 13 C moiety, is cleaved to obtain the metabolite of interest. The reported procedure can be extended to a number of other biologically relevant substrates.

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“…This route shows great potential for enhancing both analytical NMR and clinical diagnosis in the future (17)(18)(19)(20)(21)(22). SABRE does not change the chemical identity of the agent it hyperpolarizes but equilibrates polarization between p-H 2 and the selected agent through binding to an iridium center (23).…”

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confidence: 99%

Delivering strong ¹ H nuclear hyperpolarization levels and long magnetic lifetimes through signal amplification by reversible exchange

Rayner

Burns

Olaru

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Hyperpolarization turns typically weak NMR and MRI responses into strong signals so that ordinarily impractical measurements become possible. The potential to revolutionize analytical NMR and clinical diagnosis through this approach reflect this area's most compelling outcomes. Methods to optimize the low-cost parahydrogen-based approach signal amplification by reversible exchange with studies on a series of biologically relevant nicotinamides and methyl nicotinates are detailed. These procedures involve specific 2 H labeling in both the agent and catalyst and achieve polarization lifetimes of ca. 2 min with 50% polarization in the case of methyl-4,6-d 2 -nicotinate. Because a 1.5-T hospital scanner has an effective 1 H polarization level of just 0.0005% this strategy should result in compressed detection times for chemically discerning measurements that probe disease. To demonstrate this technique's generality, we exemplify further studies on a range of pyridazine, pyrimidine, pyrazine, and isonicotinamide analogs that feature as building blocks in biochemistry and many disease-treating drugs.

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Optimization of SABRE for polarization of the tuberculosis drugs pyrazinamide and isoniazid

Cited by 125 publications

References 29 publications

In Situ and Ex Situ Low‐Field NMR Spectroscopy and MRI Endowed by SABRE Hyperpolarization

In Situ and Ex Situ Low‐Field NMR Spectroscopy and MRI Endowed by SABRE Hyperpolarization

ParaHydrogen Induced Polarization of 13C carboxylate resonance in acetate and pyruvate

Delivering strong ¹ H nuclear hyperpolarization levels and long magnetic lifetimes through signal amplification by reversible exchange

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Optimization of SABRE for polarization of the tuberculosis drugs pyrazinamide and isoniazid

Cited by 125 publications

References 29 publications

In Situ and Ex Situ Low‐Field NMR Spectroscopy and MRI Endowed by SABRE Hyperpolarization

In Situ and Ex Situ Low‐Field NMR Spectroscopy and MRI Endowed by SABRE Hyperpolarization

ParaHydrogen Induced Polarization of 13C carboxylate resonance in acetate and pyruvate

Delivering strong 1 H nuclear hyperpolarization levels and long magnetic lifetimes through signal amplification by reversible exchange

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Delivering strong ¹ H nuclear hyperpolarization levels and long magnetic lifetimes through signal amplification by reversible exchange