TEMPO-conjugated tobacco mosaic virus as a magnetic resonance imaging contrast agent for detection of superoxide production in the inflamed liver.

Superoxide, an anionic dioxygen molecule, plays a crucial role in redox regulation within the body but is implicated in various pathological conditions when produced excessively. Efforts to develop superoxide detection strategies have led to the exploration of organic-based contrast agents for magnetic resonance imaging (MRI). This study compares the effectiveness of two such agents, nTMV-TEMPO and kTMV-TEMPO, for detecting superoxide in a mouse liver model with lipopolysaccharide (LPS)-induced inflammation.

Aggregation-induced emission luminogens for highly effective microwave dynamic therapy.

Aggregation-induced emission luminogens (AIEgens) exhibit efficient cytotoxic reactive oxygen species (ROS) generation capability and unique light-up features in the aggregated state, which have been well explored in image-guided photodynamic therapy (PDT). However, the limited penetration depth of light in tissue severely hinders AIEgens as a candidate for primary or adjunctive therapy for clinical applications. Coincidentally, microwaves (MWs) show a distinct advantage for deeper penetration depth in tissues than light.

Hyperpolarized Y-EDTMP complex as a chemical shift-based NMR sensor for pH at the physiological range.

Yttrium (III) complexes are interesting due to the similarity of their chemistry with gadolinium complexes that are used as contrast agents in nuclear magnetic resonance (NMR) spectroscopy or imaging (MRI). While most of the paramagnetic Gd-based MRI contrast agents are T or T relaxation-based sensors such as Gd-complexes for zinc or pH detection, a number of diamagnetic Y-complexes rely on changes in the chemical shift for potential quantitative MRI in biological milieu. Y, however, is a challenging nucleus to work with in conventional NMR or MRI due to its inherently low sensitivity and relatively long T relaxation time.

Supramolecular and biomacromolecular enhancement of metal-free magnetic resonance imaging contrast agents.

Many contrast agents for magnetic resonance imaging are based on gadolinium, however side effects limit their use in some patients. Organic radical contrast agents (ORCAs) are potential alternatives, but are reduced rapidly in physiological conditions and have low relaxivities as single molecule contrast agents. Herein, we use a supramolecular strategy where cucurbit[8]uril binds with nanomolar affinities to ORCAs and protects them against biological reductants to create a stable radical .

Hyperpolarized N-labeled, deuterated tris (2-pyridylmethyl)amine as an MRI sensor of freely available Zn.

Dynamic nuclear polarization (DNP) coupled with N magnetic resonance imaging (MRI) provides an opportunity to image quantitative levels of biologically important metal ions such as Zn, Mg or Ca using appropriately designed N enriched probes. For example, a Zn-specific probe could prove particularly valuable for imaging the tissue distribution of freely available Zn ions, an important known metal ion biomarker in the pancreas, in prostate cancer, and in several neurodegenerative diseases. In the present study, we prepare the cell-permeable, N-enriched, d-deuterated version of the well-known Zn chelator, tris(2-pyridylmethyl)amine (TPA) and demonstrate that the polarized ligand had favorable T and linewidth characteristics for N MRI.

Effects of glassing matrix deuteration on the relaxation properties of hyperpolarized C spins and free radical electrons at cryogenic temperatures.

Glassing matrix deuteration could be a beneficial sample preparation method for C dynamic nuclear polarization (DNP) when large electron paramagnetic resonance (EPR) width free radicals are used. However, it could yield the opposite DNP effect when samples are doped with small EPR width free radicals. Herein, we have investigated the influence of solvent deuteration on the C nuclear and electron relaxation that go along with the effects on C DNP intensities at 3.

NMR Spectroscopy Unchained: Attaining the Highest Signal Enhancements in Dissolution Dynamic Nuclear Polarization.

Dynamic nuclear polarization (DNP) via the dissolution method is one of the most successful methods for alleviating the inherently low Boltzmann-dictated sensitivity in nuclear magnetic resonance (NMR) spectroscopy. This emerging technology has already begun to positively impact chemical and metabolic research by providing the much-needed enhancement of the liquid-state NMR signals of insensitive nuclei such as C by several thousand-fold. In this Perspective, we present our viewpoints regarding the key elements needed to maximize the NMR signal enhancements in dissolution DNP, from the very core of the DNP process at cryogenic temperatures, DNP instrumental conditions, and chemical tuning in sample preparation to current developments in minimizing hyperpolarization losses during the dissolution transfer process.

Dynamic nuclear polarization of carbonyl and methyl C spins of acetate using 4-oxo-TEMPO free radical.

Hyperpolarization of C-enriched biomolecules via dissolution dynamic nuclear polarization (DNP) has enabled real-time metabolic imaging of a variety of diseases with superb specificity and sensitivity. The source of the unprecedented liquid-state nuclear magnetic resonance spectroscopic or imaging signal enhancements of >10 000-fold is the microwave-driven DNP process that occurs at a relatively high magnetic field and cryogenic temperature. Herein, we have methodically investigated the relative efficiencies of C DNP of single or double C-labeled sodium acetate with or without H-enrichment of the methyl group and using a 4-oxo-TEMPO free radical as the polarizing agent at 3.

Magnetic-Field-Dependent Lifetimes of Hyperpolarized C Spins at Cryogenic Temperature.

Using a home-built cryogen-free dynamic nuclear polarization (DNP) system with a variable magnetic field capability, C spin-lattice T relaxation times of hyperpolarized [1-C] carboxylates (sodium acetate, glycine, sodium pyruvate, and pyruvic acid) doped with trityl OX063 free radical were systematically measured for the first time at different field strengths up to 9 T at T = 1.8 K. Our data reveal that the C T values of these frozen hyperpolarized C samples vary drastically with the applied magnetic field B according to an apparent empirical power-law dependence (C T ∝ B, 2.

Transition Metal Doping Reveals Link between Electron T Reduction and C Dynamic Nuclear Polarization Efficiency.

Optimal efficiency of dissolution dynamic nuclear polarization (DNP) is essential to provide the required high sensitivity enhancements for in vitro and in vivo hyperpolarized C nuclear magnetic resonance (NMR) spectroscopy and imaging (MRI). At the nexus of the DNP process are the free electrons, which provide the high spin alignment that is transferred to the nuclear spins. Without changing DNP instrumental conditions, one way to improve C DNP efficiency is by adding trace amounts of paramagnetic additives such as lanthanide (e.

C Dynamic Nuclear Polarization Using a Trimeric Gd Complex as an Additive.

Dissolution dynamic nuclear polarization (DNP) is one of the most successful techniques that resolves the insensitivity problem in liquid-state nuclear magnetic resonance (NMR) spectroscopy and imaging (MRI) by amplifying the signal by several thousand-fold. One way to further improve the DNP signal is the inclusion of trace amounts of lanthanides in DNP samples doped with trityl OX063 free radical as the polarizing agent. In practice, stable monomeric gadolinium complexes such as Gd-DOTA or Gd-HP-DO3A are used as beneficial additives in DNP samples, further boosting the DNP-enhanced solid-state C polarization by a factor of 2 or 3.

Assembly and performance of a 6.4 T cryogen-free dynamic nuclear polarization system.

We report on the assembly and performance evaluation of a 180-GHz/6.4 T dynamic nuclear polarization (DNP) system based on a cryogen-free superconducting magnet. The DNP system utilizes a variable-field superconducting magnet that can be ramped up to 9 T and equipped with cryocoolers that can cool the sample space with the DNP assembly down to 1.

Influence of C Isotopic Labeling Location on Dynamic Nuclear Polarization of Acetate.

Dynamic nuclear polarization (DNP) via the dissolution method has alleviated the insensitivity problem in liquid-state nuclear magnetic resonance (NMR) spectroscopy by amplifying the signals by several thousand-fold. This NMR signal amplification process emanates from the microwave-mediated transfer of high electron spin alignment to the nuclear spins at high magnetic field and cryogenic temperature. Since the interplay between the electrons and nuclei is crucial, the chemical composition of a DNP sample such as the type of free radical used, glassing solvents, or the nature of the target nuclei can significantly affect the NMR signal enhancement levels that can be attained with DNP.

Construction and C hyperpolarization efficiency of a 180 GHz dissolution dynamic nuclear polarization system.

Dynamic nuclear polarization (DNP) via the dissolution method has become one of the rapidly emerging techniques to alleviate the low signal sensitivity in nuclear magnetic resonance (NMR) spectroscopy and imaging. In this paper, we report on the development and C hyperpolarization efficiency of a homebuilt DNP system operating at 6.423 T and 1.

Impact of Ho(3+)-doping on (13)C dynamic nuclear polarization using trityl OX063 free radical.

We have investigated the effects of Ho-DOTA doping on the dynamic nuclear polarization (DNP) of [1-(13)C] sodium acetate using trityl OX063 free radical at 3.35 T and 1.2 K.

C dynamic nuclear polarization using isotopically enriched 4-oxo-TEMPO free radicals.

The nitroxide-based free radical 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) is a widely used polarizing agent in NMR signal amplification via dissolution dynamic nuclear polarization (DNP). In this study, we have thoroughly investigated the effects of N and/or H isotopic labeling of 4-oxo-TEMPO free radical on C DNP of 3 M [1- C] sodium acetate samples in 1 : 1 v/v glycerol : water at 3.35 T and 1.

Hyperpolarized (13)C Magnetic Resonance and Its Use in Metabolic Assessment of Cultured Cells and Perfused Organs.

Diseased tissue is often characterized by abnormalities in intermediary metabolism. Observing these alterations in situ may lead to an improved understanding of pathological processes and novel ways to monitor these processes noninvasively in human patients. Although (13)C is a stable isotope safe for use in animal models of disease as well as human subjects, its utility as a metabolic tracer has largely been limited to ex vivo analyses employing analytical techniques like mass spectrometry or nuclear magnetic resonance spectroscopy.

Hyperpolarized 15N-pyridine derivatives as pH-sensitive MRI agents.

Highly sensitive MR imaging agents that can accurately and rapidly monitor changes in pH would have diagnostic and prognostic value for many diseases. Here, we report an investigation of hyperpolarized (15)N-pyridine derivatives as ultrasensitive pH-sensitive imaging probes. These molecules are easily polarized to high levels using standard dynamic nuclear polarization (DNP) techniques and their (15)N chemical shifts were found to be highly sensitive to pH.

Glutamine oxidation maintains the TCA cycle and cell survival during impaired mitochondrial pyruvate transport.

Alternative modes of metabolism enable cells to resist metabolic stress. Inhibiting these compensatory pathways may produce synthetic lethality. We previously demonstrated that glucose deprivation stimulated a pathway in which acetyl-CoA was formed from glutamine downstream of glutamate dehydrogenase (GDH).

Hyperpolarized 13C NMR detects rapid drug-induced changes in cardiac metabolism.

Purpose: The diseased myocardium lacks metabolic flexibility and responds to stimuli differently compared with healthy hearts. Here, we report the use of hyperpolarized 13C NMR spectroscopy to detect sudden changes in cardiac metabolism in isolated, perfused rat hearts in response to adrenergic stimulation.

Methods: Metabolism of hyperpolarized [1-(13)C]pyruvate was investigated in perfused rat hearts.

Development and performance of a 129-GHz dynamic nuclear polarizer in an ultra-wide bore superconducting magnet.

Objective: We sought to build a dynamic nuclear polarization system for operation at 4.6 T (129 GHz) and evaluate its efficiency in terms of (13)C polarization levels using free radicals that span a range of ESR linewidths.

Materials And Methods: A liquid helium cryostat was placed in a 4.

Modulation of CEST images in vivo by T1 relaxation: a new approach in the design of responsive PARACEST agents.

A novel approach for the design of responsive paramagnetic chemical exchange saturation transfer (PARACEST) magnetic resonance imaging (MRI) agents has been developed where the signal is "turned on" by altering the longitudinal relaxation time (T1) of bulk water protons. To demonstrate this approach, a model Eu(DOTA-tetraamide) complex (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) containing two nitroxide free radical units was synthesized. The nitroxide groups substantially shortened the T1 of the bulk water protons which, in turn, resulted in quenching of the CEST signal.

Electron spin resonance studies of trityl OX063 at a concentration optimal for DNP.

We have performed temperature-dependent electron spin resonance (ESR) measurements of the stable free radical trityl OX063, an efficient polarizing agent for dissolution dynamic nuclear polarization (DNP), at the optimum DNP concentration (15 mM). We have found that (i) when compared to the W-band electron spin-lattice relaxation rate T1e(-1) of other free radicals used in DNP at the same concentration, trityl OX063 has slower T1e(-1) than BDPA and 4-oxo-TEMPO. At T > 20 K, the T1e(-1)vs.