Production of Pure Aqueous <sup>13</sup>C‐Hyperpolarized Acetate by Heterogeneous Parahydrogen‐Induced Polarization

Kovtunov, Kirill V.; Barskiy, Danila A.; Shchepin, Roman V.; Salnikov, Oleg G.; Prosvirin, Igor P.; Bukhtiyarov, Andrey V.; Kovtunova, Larisa M.; Bukhtiyarov, Valerii I.; Koptyug, Igor V.; Chekmenev, Eduard Y.

doi:10.1002/chem.201603974

Cited by 39 publications

(60 citation statements)

References 48 publications

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“…The use of a supported catalyst would allow to obtain complete removal of the toxic metal from the solution of the hyperpolarized product and to recover the expensive catalyst, and the development of these catalysts will be an important step towards the clinical translation perspective. [22] In this work, the phase transfer method has been applied. [23] According to this procedure, the lipophylic substrate is hydrogenated in an organic, hydrophobic solvent, (e.g.…”

Section: Hyperpolarized L-[1-c]lactatementioning

confidence: 99%

¹³C MR Hyperpolarization of Lactate by Using ParaHydrogen and Metabolic Transformation in Vitro

Cavallari

Carrera

Aime

et al. 2016

Chemistry A European J

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Abstract:Hyperpolarization of the 13C magnetic resonance signal of L-[1-13C]Lactate has been obtained using the chemically based, cost-effective method named ParaHydrogen Induced Polarization by means of Side Arm Hydrogenation (PHIP-SAH). Two ester derivatives of lactate have been tested and the factors that determine the polarization level on the product have been investigated into details. The metabolic conversion of hyperpolarized L-[1-13C]Lactate into Pyruvate has been observed in vitro using lactate dehydrogenase (LDH) and in a cells lysate. From the acquisition of a series of 13C-NMR spectra, the metabolic build-up of the [1-13C]Pyruvate signal has been observed. These studies demonstrate that, even if the experimental set-up used for these PHIP-SAH hyperpolarization studies is still far from optimal, the attained polarization level is already sufficient to carry out in vitro metabolic studies.Author Comments: Dear editor, enclosed please find the manuscript entitled "13C-MR Hyperpolarization of Lactate using ParaHydrogen and metabolic transformation in vitro " to be considered for publication in Chemistry, a European Journal. A previous version of the manuscript had been submitted to this journal and one of the two referees evaluated it a highly important manuscript, while the other considered it too specialized for publication, than the manuscript was rejected. Nevertheless, the editor suggested that an appropriately supplemented manuscript should be reconsidered.Here is submitted a deeply revised version of the manuscript. New experiments have been added, in accordance with the reviewers' suggestions, and new results have been obtained. The whole text has been extensively edited and integrated. We hope that, with the integration of the new results, the manuscript will be considered worth of publication in Chemistry. C]Pyruvate signal has been observed. These studies demonstrate that, even if the experimental set-up used for these PHIP-SAH hyperpolarization studies is still far from optimal, the attained polarization level is already sufficient to carry out in vitro metabolic studies. Yours sincerely Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation

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Section: Hyperpolarized L-[1-c]lactatementioning

confidence: 99%

¹³C MR Hyperpolarization of Lactate by Using ParaHydrogen and Metabolic Transformation in Vitro

Cavallari

Carrera

Aime

et al. 2016

Chemistry A European J

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“…The equipment was tested on the parahydrogen addition product of 2-hydroxyethyl acrylate-1- 13 C- d 3 , whereupon conversion of the initial singlet state of nascent protons to net heteronuclear magnetization, 13 C polarization P was estimated to be 20 % ± 2.5 % corresponding to 13 C signal enhancement of approximately 25-million-fold at this reference low field of 9.1 mT or approximately 77,000-fold at 3 T with respect to thermally induced polarization at room temperature. The central control of the hyperpolarization could also be useful for non-hydrogenative PHIP experiments [43, 64, 78–80] as well as in the context heterogeneous PHIP experiments [81, 82]. For biomedical applications, we anticipate that this design will be especially useful to laboratories already equipped with low field imaging consoles, and additionally, for basic science applications this polarizer design should facilitate translation of PASADENA to multidimensional NMR experiments.…”

Section: Discussionmentioning

confidence: 99%

A pulse programmable parahydrogen polarizer using a tunable electromagnet and dual channel NMR spectrometer

Coffey

Shchepin

Feng

et al. 2017

Journal of Magnetic Resonance

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Applications of parahydrogen induced polarization (PHIP) often warrant conversion of the chemically-synthesized singlet-state spin order into net heteronuclear magnetization. In order to obtain optimal yields from the overall hyperpolarization process, catalytic hydrogenation must be tightly synchronized to subsequent radiofrequency (RF) transformations of spin order. Commercial NMR consoles are designed to synchronize applied waves on multiple channels and consequently are well-suited as controllers for these types of hyperpolarization experiments that require tight coordination of RF and non-RF events. Described here is a PHIP instrument interfaced to a portable NMR console operating with a static field electromagnet in the milliTesla regime. In addition to providing comprehensive control over chemistry and RF events, this setup condenses the PHIP protocol into a pulse-program that in turn can be readily shared in the manner of traditional pulse sequences. In this device, a TTL multiplexer was constructed to convert spectrometer TTL outputs into 24 VDC signals. These signals then activated solenoid valves to control chemical shuttling and reactivity in PHIP experiments. Consolidating these steps in a pulse-programming environment speeded calibration and improved quality assurance by enabling the B0/B1 fields to be tuned based on the direct acquisition of thermally polarized and hyperpolarized NMR signals. Performance was tested on the parahydrogen addition product of 2-hydroxyethyl propionate-1-13C-d3, where the 13C polarization was estimated to be P13C = 20 ± 2.5 % corresponding to 13C signal enhancement approximately 25 million-fold at 9.1 mT or approximately 77,000-fold 13C enhancement at 3 T with respect to thermally induced polarization at room temperature.

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“…In the case of lactate, it was demonstrated that, after the polarization procedure, lactate can enzymatically be converted into pyruvate . So far, the most successful approach of hyperpolarizing metabolites with para ‐hydrogen relies on a field cycling technique, for which 13 C polarization values of about 5 % have been experimentally demonstrated in highly concentrated solutions of acetate and pyruvate . The theoretical polarization limits of the field cycling technique have been investigated and simulations for an ideal case have shown that more than 30 % 13 C polarization can be achieved in the precursor molecule (before cleavage), whereas 50 % was suggested experimentally …”

Section: Figurementioning

confidence: 99%

Over 50 % ¹H and ¹³C Polarization for Generating Hyperpolarized Metabolites—A para‐Hydrogen Approach

2018

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para‐Hydrogen‐induced polarization (PHIP) is a method to rapidly generate hyperpolarized compounds, enhancing the signal of nuclear magnetic resonance (NMR) experiments by several thousand‐fold. The hyperpolarization of metabolites and their use as contrast agents in vivo is an emerging diagnostic technique. High degrees of polarization and extended polarization lifetime are necessary requirements for the detection of metabolites in vivo. Here, we present pulsed NMR methods for obtaining hyperpolarized magnetization in two metabolites. We demonstrate that the hydrogenation with para‐hydrogen of perdeuterated vinyl acetate allows us to create hyperpolarized ethyl acetate with close to 60 % 1H two‐spin order. With nearly 100 % efficiency, this order can either be transferred to 1H in‐phase magnetization or 13C magnetization of the carbonyl function. Close to 60 % polarization is experimentally verified for both nuclei. Cleavage of the ethyl acetate precursor in a 20 s reaction yields ethanol with approximately 27 % 1H polarization and acetate with around 20 % 13C polarization. This development will open new opportunities to generate metabolic contrast agents in less than one minute.

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Production of Pure Aqueous ¹³C‐Hyperpolarized Acetate by Heterogeneous Parahydrogen‐Induced Polarization

Cited by 39 publications

References 48 publications

¹³C MR Hyperpolarization of Lactate by Using ParaHydrogen and Metabolic Transformation in Vitro

¹³C MR Hyperpolarization of Lactate by Using ParaHydrogen and Metabolic Transformation in Vitro

A pulse programmable parahydrogen polarizer using a tunable electromagnet and dual channel NMR spectrometer

Over 50 % ¹H and ¹³C Polarization for Generating Hyperpolarized Metabolites—A para‐Hydrogen Approach

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Production of Pure Aqueous 13C‐Hyperpolarized Acetate by Heterogeneous Parahydrogen‐Induced Polarization

Cited by 39 publications

References 48 publications

13C MR Hyperpolarization of Lactate by Using ParaHydrogen and Metabolic Transformation in Vitro

13C MR Hyperpolarization of Lactate by Using ParaHydrogen and Metabolic Transformation in Vitro

A pulse programmable parahydrogen polarizer using a tunable electromagnet and dual channel NMR spectrometer

Over 50 % 1H and 13C Polarization for Generating Hyperpolarized Metabolites—A para‐Hydrogen Approach

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Production of Pure Aqueous ¹³C‐Hyperpolarized Acetate by Heterogeneous Parahydrogen‐Induced Polarization

¹³C MR Hyperpolarization of Lactate by Using ParaHydrogen and Metabolic Transformation in Vitro

¹³C MR Hyperpolarization of Lactate by Using ParaHydrogen and Metabolic Transformation in Vitro

Over 50 % ¹H and ¹³C Polarization for Generating Hyperpolarized Metabolites—A para‐Hydrogen Approach