Nuclear spin hyperpolarization of pyruvate enables longitudinal monitoring of treatment response in intestinal tumor organoids DOI Creative Commons
Josh Peters,

Xiang Hang,

Charbel D. Assaf

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Дек. 25, 2024

Abstract Colorectal cancer, a leading cause of death in the Western world, is increasingly affecting younger populations. The Warburg effect, characterized by enhanced lactate production, hallmark this cancer type. While 18F-FDG PET-CT commonly used for diagnosis, magnetic resonance imaging (MRI) offers higher spatial and chemical resolution without drawbacks radiation. However, MRI's low sensitivity has been barrier to real-time metabolic imaging, hence implementation into clinical practice. Hyperpolarization significantly boosted NMR sensitivity, enabling detailed studies vivo. This study utilizes hyperpolarized [1-13C]pyruvate with dissolution dynamic nuclear polarization (dDNP) non-invasively monitor changes intestinal organoids from genetically defined mouse model spontaneous carcinogenesis (Rnaseh2b/Xbp1ΔIEC) previously established targeted therapeutic intervention (mTOR inhibition rapamycin). Hyperpolarized revealed significant reduction production rapamycin-treated organoids, indicating suppressed activity. method also detected alanine bicarbonate metabolism, highlighting its sensitivity. Unlike traditional methods that destroy cellular integrity, hyperpolarization enables repetitive, non-invasive assessments, bridging gap between preclinical applications affirming method's potential as novel diagnostic treatment control approach medicine.

Язык: Английский

Zero to ultralow magnetic field NMR of [1−13C]pyruvate and [2 DOI Creative Commons
John Z. Myers,

Friedemann Bullinger,

Nicolas Kempf

и другие.

Physical review. B./Physical review. B, Год журнала: 2024, Номер 109(18)

Опубликована: Май 30, 2024

Accurately characterizing magnetic resonance of molecules at zero to ultralow field (nTs-µTs) is challenging, due vanishingly small sensitivity, which depends on the thermal equilibrium polarization nuclear spins and instrumentation. We overcome former limitation with parahydrogen-based hyperpolarization method SABRE-SHEATH (signal amplification by reversible exchange in shield enables alignment transfer heteronuclei). This allows for continuous spin order from parahydrogen a substrate via chemical exchange, reaching levels some percent (level equivalent C13 20 kT). address latter our application superconducting quantum interference device (SQUID)-based detector setup that broadband detection (dc-MHz) exquisite sensitivity over its entire range. Here, we present results comprehensive characterization [1−13C]pyruvate [2−13C]pyruvate, hyperpolarized SABRE-SHEATH, 100 µT. To this end, show low-noise, high-resolution spectra both molecules, detecting how NMR spectrum changes -coupling dominated zero-field strongly coupled spectrum, then finally conventional high-field, otherwise known Zeeman-dominated spectrum. also analytically derive evolution product operators arbitrary fields, aid understanding differences between spin-coupling regimes. predict confirm absence precession can result observable oscillation magnetization along one axis frequency constant, no evolution, or observing corresponds “forbidden” transitions high field. The their near-dc signals reveal different relaxation rates states C13 pyruvates, demonstrating utility SQUID detectors phenomena. Published American Physical Society 2024

Язык: Английский

Процитировано

5
Toward Next-Generation Molecular Imaging with a Clinical Low-Field (0.064 T) Point-of-Care MRI Scanner DOI

N Iqbal,

Drew O. Brittin,

Praveen J. Daluwathumullagamage

и другие.

Analytical Chemistry, Год журнала: 2024, Номер 96(25), С. 10348 - 10355

Опубликована: Июнь 10, 2024

Low-field (LF) MRI promises soft-tissue imaging without the expensive, immobile magnets of clinical scanners but generally suffers from limited detection sensitivity and contrast. The boost provided by hyperpolarization can thus be highly synergistic with LF MRI. Initial efforts to integrate a continuous-bubbling SABRE (signal amplification reversible exchange) setup portable, point-of-care 64 mT scanner are reported. Results 1H pyrazine nicotinamide compared those benchtop NMR spectroscopy. Comparison signals samples known H2O/D2O ratios allowed quantification enhancements imaged various substrate concentrations (down 3 mM). Respective limits 3.3 10.1 mM were determined polarization (PH) ∼1900 (PH ∼0.04%), supporting ongoing envisioned realize SABRE-enabled MRI-based molecular imaging.

Язык: Английский

Процитировано

2
Cross-Polarization of Insensitive Nuclei from Water Protons for Detection of Protein–Ligand Binding DOI Creative Commons
Nirmalya Pradhan, Christian Hilty

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(36), С. 24754 - 24758

Опубликована: Сен. 3, 2024

Hyperpolarization derived from water protons enhances the NMR signal of

Язык: Английский

Процитировано

2
Hyperpolarization of 15N‐Pyridinium by Using Parahydrogen Enables Access to Reactive Oxygen Sensors and Pilot In Vivo Studies DOI Creative Commons
Ruhuai Mei, Lisa M. Fries,

Theresa L. K. Hune

и другие.

Angewandte Chemie International Edition, Год журнала: 2024, Номер unknown

Опубликована: Май 22, 2024

Magnetic resonance with hyperpolarized contrast agents is one of the most powerful and noninvasive imaging platforms capable for investigating in vivo metabolism. While utilized are based on

Язык: Английский

Процитировано

2
Yeast Solutions and Hyperpolarization Enable Real-Time Observation of Metabolized Substrates Even at Natural Abundance DOI Creative Commons
Josh Peters, Charbel D. Assaf, Farhad Haj Mohamad

и другие.

Analytical Chemistry, Год журнала: 2024, Номер 96(43), С. 17135 - 17144

Опубликована: Окт. 15, 2024

Metabolic changes in an organism often occur much earlier than macroscopic manifestations of disease, such as invasive tumors. Therefore, noninvasive tools to monitor metabolism are fundamental they provide insights into vivo biochemistry. NMR represents one the gold standards for by observing metabolites. Using nuclear spin hyperpolarization greatly increases sensitivity, enabling μmol/L sensitivity with a time resolution about second. However, metabolic phantom reproducible, rapid, and human-like is needed progress research this area. baker's yeast convenient factory, we demonstrated single study that cells robust rapidly metabolizing pyruvate fumarate, including substrates natural abundance

Язык: Английский

Процитировано

1
Hyperpolarization of 15N‐Pyridinium by Using Parahydrogen Enables Access to Reactive Oxygen Sensors and Pilot In Vivo Studies DOI Creative Commons
Ruhuai Mei, Lisa M. Fries,

Theresa L. K. Hune

и другие.

Angewandte Chemie, Год журнала: 2024, Номер unknown

Опубликована: Май 22, 2024

Abstract Magnetic resonance with hyperpolarized contrast agents is one of the most powerful and noninvasive imaging platforms capable for investigating in vivo metabolism. While utilized are based on 13 C nuclei, a milestone advance this area emergence 15 N agents. Currently, reported mainly utilize dissolution dynamic nuclear polarization (d‐DNP) protocol. The parahydrogen enhanced probes have proven to be elusive been tested almost exclusively organic solvents. Herein, we designed reaction reactive oxygen sensor N‐boronobenzyl‐2‐styrylpyridinium ( N‐BBSP) which can para‐hydrogen. Reactive species plays vital role as essential intracellular signalling molecules. Disturbance H 2 O level usually represents hallmark pathophysiological conditions. This probe exhibited rapid responsiveness toward offered spectrally resolvable chemical shifts. We also provide strategies bring newly developed from solution into biocompatible injection buffer demonstrate feasibility signal detection. present work manifests its great potential not only sensing but promises serve platform develop other

Язык: Английский

Процитировано

0
Chemically induced deceleration of nuclear spin relaxation (CIDER) preserves hyperpolarization DOI
Josh Peters, Charbel D. Assaf, Arne Brahms

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Июль 11, 2024

Abstract The hyperpolarization of nuclear spins has enabled real-time molecular magnetic resonance imaging. Hyperpolarized tracers like pyruvate have visualization metabolism in vitro and vivo. However, the scope hyperpolarizable molecules remains limited. We found that specific such as 15N-pyridine, 1-15N-nicotinamide, 15N-nicotinic acid can be hyperpolarized well using dynamic polarization; however, polarization does not persist after dissolution. primary contribution to this swift relaxation is a rapid chemical exchange protons possibly other interactions, which accelerate at low fields. discovered adding molecules, nicotinamide, urea, nicotinic acid, glycerol dissolution medium, protected from dramatically improved 15N polarization. This chemically induced deceleration spin (CIDER) effect allowed us observe highest reported literature so far, almost 30% for biomolecule 1-15N nicotinamide. anticipate CIDER will very useful prolong T1 various thereby extending boundaries imaging beyond.

Язык: Английский

Процитировано

0
Analysis of Chemical Exchange in Iridium N-Heterocyclic Carbene Complexes Using Heteronuclear Parahydrogen-Enhanced NMR DOI Creative Commons
Charbel D. Assaf, Xin Gui, Oleg G. Salnikov

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Авг. 23, 2024

Abstract The signal amplification by reversible exchange process (SABRE) amplifies NMR signals unlocking hidden polarization in parahydrogen through interactions with to-be-hyperpolarized substrate molecules when both are transiently bound to an Ir-based organometallic catalyst. Recent efforts have focused on optimizing the transfer step from parahydrogen-derived hydride ligands SABRE. However, this requires quantitative information ligand rates, which common techniques struggle provide. Here, we introduce experimental spin order sequence where readout occurs at 15N nuclei directly interacting To overcome sensitivity challenges, enhanced created, encoding discrete dissociation rates. This methodology enables robust data fitting proposed models, yielding rate constants higher precision than classical 1D and 2D 1H approaches. refinement provides accuracy for estimating key activation enthalpy ΔH‡ ΔS‡. Moreover, chemical shift dispersion provided signal-enhanced allows kinetics of acetonitrile metronidazole, previously inaccessible via due small differences between resonances free Ir-bound these substrates.

Язык: Английский

Процитировано

0
Hyperpolarised benchtop NMR spectroscopy for analytical applications DOI Creative Commons
Ana I. Silva Terra, Daniel A. Taylor, Meghan E. Halse

и другие.

Progress in Nuclear Magnetic Resonance Spectroscopy, Год журнала: 2024, Номер 144-145, С. 153 - 178

Опубликована: Окт. 23, 2024

Язык: Английский

Процитировано

0
Analysis of chemical exchange in iridium N-heterocyclic carbene complexes using heteronuclear parahydrogen-enhanced NMR DOI Creative Commons
Charbel D. Assaf, Xin Gui, Oleg G. Salnikov

и другие.

Communications Chemistry, Год журнала: 2024, Номер 7(1)

Опубликована: Дек. 3, 2024

Abstract The signal amplification by reversible exchange process (SABRE) enhances NMR signals unlocking hidden polarization in parahydrogen through interactions with to-be-hyperpolarized substrate molecules when both are transiently bound to an Ir-based organometallic catalyst. Recent efforts focus on optimizing transfer from parahydrogen-derived hydride ligands the SABRE. However, this requires quantitative information ligand rates, which common techniques struggle provide. Here, we introduce experimental spin order sequence, readout occurring at 15 N nuclei directly interacting Enhanced overcome sensitivity challenges, encoding dissociation rates. This methodology enables robust data fitting models, yielding rate constants higher precision than classical 1D and 2D 1 H approaches. refinement improves accuracy of key activation enthalpy ΔH ‡ entropy ΔS estimates. Furthermore, chemical shift dispersion provided enhanced reveals kinetics for acetonitrile metronidazole, previously inaccessible via due small differences between free Ir-bound substrates. presented approach can be successfully applied not only isotopically enriched substrates but also compounds natural abundance heteronuclei.

Язык: Английский

Процитировано

0