Real-Time Pyruvate Chemical Conversion Monitoring Enabled by PHIP

Stevanato, Gabriele; Ding, Yong; Mamone, Salvatore; Jagtap, Anil P.; Korchak, Sergey; Glöggler, Stefan

doi:10.1021/jacs.2c13198

Cited by 14 publications

(6 citation statements)

References 65 publications

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“…This spin order is transferred to the molecule of interest by a method, which is called parahydrogen-induced polarization by means of side-arm hydrogenation (PHIP-SAH) [22]. Since its introduction in 2015 by Reineri et al, it has found broad application [23][24][25][26][27][28][29][30][31][32]. The workflow applied here is depicted in Fig.…”

Section: Applied Magnetic Resonancementioning

confidence: 99%

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Hyperpolarized Multi-organ Spectroscopy of Liver and Brain Using 1-13C-Pyruvate Enhanced via Parahydrogen

Hune,

Mamone,

Schmidt

et al. 2023

Appl Magn Reson

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Hyperpolarization in nuclear magnetic resonance boosts the signals by several orders of magnitude. Using the singlet spin order of parahydrogen to create large non-equilibrium spin polarization is a fast approach to obtain hyperpolarized metabolites in seconds. In recent years, it has attracted particular interest in the field of biomedicine because signal-enhanced and 13C-enriched metabolites allow for real-time metabolic investigations in combination with imaging in vivo. With this, metabolism can be traced and characterized with spatial selectivity in the body. Here, we introduce a method to use signal-enhanced metabolites to study multiple organs in separate injections to obtain real-time kinetics in vivo of these organs. Using hyperpolarized 1-13C-pyruvate, we measured the kinetics of the conversion from pyruvate to lactate in the brain and the liver of mice. This we did by injecting the hyperpolarized pyruvate two times within half an hour and using each injection to measure the spectra of one region of interest. Organ cross-talk and especially how different organs affect each other in diseases is of major interest and poorly understood, because of the high complexity of biological systems. With the proof-of-principle study provided here, we are introducing a new tool to study organ-related interaction in vivo. It allows the characterization of different organs of the same animal within half an hour, which is enabled by the fast signal enhancement achieved with parahydrogen.

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Section: Applied Magnetic Resonancementioning

confidence: 99%

“…The aqueous 1 3 Hyperpolarized Multi-organ Spectroscopy of Liver and Brain… solution containing clean hyperpolarized pyruvate was ready to be injected. A more detailed description on the procedure was previously described [31][32][33].…”

Section: Hyperpolarizationmentioning

confidence: 99%

Hyperpolarized Multi-organ Spectroscopy of Liver and Brain Using 1-13C-Pyruvate Enhanced via Parahydrogen

Hune,

Mamone,

Schmidt

et al. 2023

Appl Magn Reson

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“…28 Alkyne esters represent an important class of targets as they offer the possibly to hyperpolarize a range of carboxylate containing molecules such as pyruvate or lactate via the side-arm hydrogenation (PHIP-SAH) strategy. [29][30][31][32] Here we study the production of hyperpolarized allyl acetate (AL) as shown in Fig. 1a.…”

Section: Introductionmentioning

confidence: 99%

Efficient Parahydrogen Induced 13C Hyperpolarization on a Microfluidic Device

Barker,

Dagys,

Levitt

et al. 2024

Preprint

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In this work we demonstrate the direct production and detection of carbon-hyperpolarized fumarate by parahydrogen-induced polarization (PHIP) in a microfluidic Lab-on-a-Chip (LoC) device and achieve 8.5% 13C polarization. This is the first demonstration of 13C-hyperpolarization of a metabolite by PHIP in a microfluidic device. LoC technology allows the culture of mammalian cells in a highly controlled environment, providing an important tool for the life sciences. In-situ preparation of hyperpolarized metabolites greatly enhances the ability to quantify metabolic processes in such systems by microfluidic NMR. PHIP of 1H nuclei has been successfully implemented in microfluidic systems, with mass sensitivities in the range of pmol/√s but only with low yields. Metabolic NMR requires high-yield production of hyperpolarized metabolites with longer spin life times than is possible with1H. This can be achieved by transfer of the polarization onto 13C nuclei, which exhibit much longer T1 relaxation times. We report an improved microfluidic PHIP device that has been optimised using a finite element model that achieves a more than 20-fold improvement in the yield of the hyperpolarized product. It is shown that this enables detailed kinetic studies of the hydrogenation of propargyl acetate to allyl acetate, as well as the direct production of 13C hyperpolarized fumarate.

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“…A faster and simpler approach to hyperpolarize [1-13 C]pyruvate is parahydrogen-induced polarization (PHIP). 38,[51][52][53] One possibility is side-arm hydrogenation PHIP (SAH-PHIP), 54,55 which has been successfully used to hyperpolarize [1-13C]pyruvate, [56][57][58] the most common hyperpolarized MRI tracer. In SAH-PHIP an unsaturated side arm of a pyruvate ester is hydrogenated with parahydrogen, the polarization is transferred to the 13 C nucleus, and the pyruvate is then cleaved via hydrolysis of the ester.…”

Section: Introductionmentioning

confidence: 99%

Facile hyperpolarization chemistry for molecular imaging and metabolic tracking of [1-13C]pyruvate in vivo

Browning

MacCulloch

Bedoya

et al. 2023

Preprint

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Hyperpolarization chemistry based on reversible exchange of parahydrogen, also known as Signal Amplification By Reversible Exchange (SABRE), is a particularly simple approach to attain high levels of nuclear spin hyperpolarization, which can enhance NMR and MRI signals by many orders of magnitude. SABRE has received significant attention in the scientific community since its inception because of its relative experimental simplicity and its broad applicability to a wide range of molecules, however in vivo detection of molecular probes hyperpolarized by SABRE has remained elusive. Here we describe the first demonstration of SABRE-hyperpolarized contrast detected in vivo, specifically using hyperpolarized [1-13C]pyruvate. A biocompatible formulation of hyperpolarized [1-13C]pyruvate was injected into healthy Sprague Dawley and Wistar rats, and metabolic conversion of pyruvate to lactate, alanine, pyruvate-hydrate, and bicarbonate was detected. Measurements were performed on the liver and kidney at 4.7 T via time-resolved spectroscopy and chemical-shift-resolved MRI. In addition, whole-body metabolic measurements were obtained using a cryogen-free 1.5 T MRI system, illustrating the utility of combining lower-cost MRI systems with simple, low-cost hyperpolarization chemistry to develop scalable, next-generation molecular imaging.

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Real-Time Pyruvate Chemical Conversion Monitoring Enabled by PHIP

Cited by 14 publications

References 65 publications

Hyperpolarized Multi-organ Spectroscopy of Liver and Brain Using 1-13C-Pyruvate Enhanced via Parahydrogen

Hyperpolarized Multi-organ Spectroscopy of Liver and Brain Using 1-13C-Pyruvate Enhanced via Parahydrogen

Efficient Parahydrogen Induced 13C Hyperpolarization on a Microfluidic Device

Facile hyperpolarization chemistry for molecular imaging and metabolic tracking of [1-13C]pyruvate in vivo

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