SABRE-SHEATH Hyperpolarization of [1,5-C]Z-OMPD for Noninvasive pH Sensing.

Hyperpolarized (HP) C-labeled probes are emerging as promising agents to noninvasively image pH in vivo. HP [1,5-C]Z-OMPD (Z-4-methyl-2-oxopent-3-enedioic acid) in particular has recently been used to simultaneously report on kidney perfusion, filtration, and pH homeostasis, in addition to the ability to detect local tumor acidification. In previous studies, dissolution dynamic nuclear polarization was used to hyperpolarize Z-OMPD.

Carbon-13 Hyperpolarization of α-Ketocarboxylates with Parahydrogen in Reversible Exchange.

Signal Amplification by Reversible Exchange (SABRE) is a relatively simple and fast hyperpolarization technique that has been used to hyperpolarize the α-ketocarboxylate pyruvate, a central metabolite and the leading hyperpolarized MRI contrast agent. In this work, we show that SABRE can readily be extended to hyperpolarize C nuclei at natural abundance on many other α-ketocarboxylates. Hyperpolarization is observed and optimized on pyruvate (P=17 %) and 2-oxobutyrate (P=25 %) with alkyl chains in the R-group, oxaloacetate (P=11 %) and alpha-ketoglutarate (P=13 %) with carboxylate moieties in the R group, and phenylpyruvate (P=2 %) and phenylglyoxylate (P=2 %) with phenyl rings in the R-group.

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

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 a first demonstration of SABRE-hyperpolarized contrast detected in vivo, specifically using hyperpolarized [1-C]pyruvate.

Spin dynamics of [1,2-C]pyruvate hyperpolarization by parahydrogen in reversible exchange at micro Tesla fields.

Hyperpolarization of C-pyruvate Signal Amplificaton By Reversibble Exchange (SABRE) is an important recent discovery because of both the relative simplicity of hyperpolarization and the central biological relevance of pyruvate as a biomolecular probe for or studies. Here, we analyze the [1,2-C]pyruvate-SABRE spin system and its field dependence theoretically and experimentally. We provide first-principles analysis of the governing 4-spin dihydride-C Hamiltonian and numerical spin dynamics simulations of the 7-spin dihydride-C-CH system.

Parahydrogen in Reversible Exchange Induces Long-Lived N Hyperpolarization of Anticancer Drugs Anastrozole and Letrozole.

Hyperpolarization modalities overcome the sensitivity limitations of NMR and unlock new applications. Signal amplification by reversible exchange (SABRE) is a particularly cheap, quick, and robust hyperpolarization modality. Here, we employ SABRE for simultaneous chemical exchange of parahydrogen and nitrile-containing anticancer drugs (letrozole or anastrozole) to enhance N polarization.

Interplay of Near-Zero-Field Dephasing, Rephasing, and Relaxation Dynamics and [1-C]Pyruvate Polarization Transfer Efficiency in Pulsed SABRE-SHEATH.

Hyperpolarized [1-C]pyruvate is a revolutionary molecular probe enabling ultrafast metabolic MRI scans in 1 min. This technology is now under evaluation in over 30 clinical trials, which employ dissolution Dynamic Nuclear Polarization (d-DNP) to prepare a batch of the contrast agent; however, d-DNP technology is slow and expensive. The emerging SABRE-SHEATH hyperpolarization technique enables fast (under 1 min) and robust production of hyperpolarized [1-C]pyruvate via simultaneous chemical exchange of parahydrogen and pyruvate on IrIMes hexacoordinate complexes.

Triplet Photosensitized -Hydrogen Induced Polarization.

Despite its enormous utility in structural characterization, nuclear magnetic resonance (NMR) spectroscopy is inherently limited by low spin polarization. One method to address the low polarization is -hydrogen (-H) induced polarization (PHIP) which uses the singlet spin isomer of H to generate disparate nuclear spin populations to amplify the associated NMR signals. PHIP often relies on thermal catalysis or, more infrequently, UV-activated catalytic hydrogenation.

Catalyst-Free Aqueous Hyperpolarized [1-C]Pyruvate Obtained by Re-Dissolution Signal Amplification by Reversible Exchange.

Despite great successes in oncology, patient outcomes are often still discouraging, and hence the diagnostic imaging paradigm is increasingly shifting toward functional imaging of the pathology to better understand individual disease biology and to personalize therapies. The dissolution Dynamic Nuclear Polarization (d-DNP) hyperpolarization method has enabled unprecedented real-time MRI sensing of metabolism and tissue pH using hyperpolarized [1-C]pyruvate as a biosensor with great potential for diagnosis and monitoring of cancer patients. However, current d-DNP is expensive and suffers from long hyperpolarization times, posing a substantial translational roadblock.

Temperature Cycling Enables Efficient C SABRE-SHEATH Hyperpolarization and Imaging of [1-C]-Pyruvate.

Molecular metabolic imaging in humans is dominated by positron emission tomography (PET). An emerging nonionizing alternative is hyperpolarized MRI of C-pyruvate, which is innocuous and has a central role in metabolism. However, similar to PET, hyperpolarized MRI with dissolution dynamic nuclear polarization (d-DNP) is complex costly, and requires significant infrastructure.

Order-Unity C Nuclear Polarization of [1- C]Pyruvate in Seconds and the Interplay of Water and SABRE Enhancement.

Signal Amplification By Reversible Exchange in SHield Enabled Alignment Transfer (SABRE-SHEATH) is investigated to achieve rapid hyperpolarization of C spins of [1- C]pyruvate, using parahydrogen as the source of nuclear spin order. Pyruvate exchange with an iridium polarization transfer complex can be modulated via a sensitive interplay between temperature and co-ligation of DMSO and H O. Order-unity C (>50 %) polarization of catalyst-bound [1- C]pyruvate is achieved in less than 30 s by restricting the chemical exchange of [1- C]pyruvate at lower temperatures.

Density Functional Theory Study of Reaction Equilibria in Signal Amplification by Reversible Exchange.

The front cover artwork is provided by the groups of Prof. Thomas Theis (North Carolina State University) Prof. Volker Blum (Duke University).

A Versatile Compact Parahydrogen Membrane Reactor.

We introduce a Spin Transfer Automated Reactor (STAR) that produces continuous parahydrogen induced polarization (PHIP), which is stable for hours to days. We use the PHIP variant called signal amplification by reversible exchange (SABRE), which is particularly well suited to produce continuous hyperpolarization. The STAR is operated in conjunction with benchtop (1.

Density Functional Theory Study of Reaction Equilibria in Signal Amplification by Reversible Exchange.

An in-depth theoretical analysis of key chemical equilibria in Signal Amplification by Reversible Exchange (SABRE) is provided, employing density functional theory calculations to characterize the likely reaction network. For all reactions in the network, the potential energy surface is probed to identify minimum energy pathways. Energy barriers and transition states are calculated, and harmonic transition state theory is applied to calculate exchange rates that approximate experimental values.

Hyperpolarization of common antifungal agents with SABRE.

Signal amplification by reversible exchange (SABRE) is a robust and inexpensive hyperpolarization (HP) technique to enhance nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI) signals using parahydrogen (pH ). The substrate scope of SABRE is continually expanding. Here, we present the polarization of three antifungal drugs (voriconazole, clotrimazole, and fluconazole) and elicit the detailed HP mechanisms for H and N nuclei.

Automated pneumatic shuttle for magnetic field cycling and parahydrogen hyperpolarized multidimensional NMR.

We present a simple-to-implement pneumatic sample shuttle for automation of magnetic field cycling and multidimensional NMR. The shuttle system is robust allowing automation of hyperpolarized and non-hyperpolarized measurements, including variable field lifetime measurements, SABRE polarization optimization, and SABRE multidimensional experiments. Relaxation-protected singlet states are evaluated by variable-field T and T measurements.