Synthetic Approaches for N-Labeled Hyperpolarized Heterocyclic Molecular Imaging Agents for N NMR Signal Amplification by Reversible Exchange in Microtesla Magnetic Fields.

NMR hyperpolarization techniques enhance nuclear spin polarization by several orders of magnitude resulting in corresponding sensitivity gains. This enormous sensitivity gain enables new applications ranging from studies of small molecules by using high-resolution NMR spectroscopy to real-time metabolic imaging in vivo. Several hyperpolarization techniques exist for hyperpolarization of a large repertoire of nuclear spins, although the C and N sites of biocompatible agents are the key targets due to their widespread use in biochemical pathways.

PHIP hyperpolarized [1-C]pyruvate and [1-C]acetate esters via PH-INEPT polarization transfer monitored by C NMR and MRI.

Parahydrogen-induced polarization of C nuclei by side-arm hydrogenation (PHIP-SAH) for [1-C]acetate and [1-C]pyruvate esters with application of PH-INEPT-type pulse sequences for H to C polarization transfer is reported, and its efficiency is compared with that of polarization transfer based on magnetic field cycling (MFC). The pulse-sequence transfer approach may have its merits in some applications because the entire hyperpolarization procedure is implemented directly in an NMR or MRI instrument, whereas MFC requires a controlled field variation at low magnetic fields. Optimization of the PH-INEPT-type transfer sequences resulted in C polarization values of 0.

N NMR Hyperpolarization of Radiosensitizing Antibiotic Nimorazole by Reversible Parahydrogen Exchange in Microtesla Magnetic Fields.

Nimorazole belongs to the imidazole-based family of antibiotics to fight against anaerobic bacteria. Moreover, nimorazole is now in Phase 3 clinical trial in Europe for potential use as a hypoxia radiosensitizer for treatment of head and neck cancers. We envision the use of [ N ]nimorazole as a theragnostic hypoxia contrast agent that can be potentially deployed in the next-generation MRI-LINAC systems.

Heterogeneous Parahydrogen-Induced Polarization of Diethyl Ether for Magnetic Resonance Imaging Applications.

Magnetic resonance imaging (MRI) with the use of hyperpolarized gases as contrast agents provides valuable information on lungs structure and function. While the technology of Xe hyperpolarization for clinical MRI research is well developed, it requires the expensive equipment for production and detection of hyperpolarized Xe. Herein we present the H hyperpolarization of diethyl ether vapor that can be imaged on any clinical MRI scanner.

Quantifying the effects of quadrupolar sinks viaN relaxation dynamics in metronidazoles hyperpolarized via SABRE-SHEATH.

N spin-lattice relaxation dynamics in metronidazole-N and metronidazole-N isotopologues are studied for rational design of N-enriched biomolecules for signal amplification by reversible exchange in microtesla fields. N relaxation dynamics mapping reveals the deleterious effects of interactions with the polarization transfer catalyst and a quadrupolar N nucleus within the spin-relayed N-N network.

F Hyperpolarization of N-3-F-Pyridine Via Signal Amplification by Reversible Exchange.

We report synthesis of N-3-F-pyridine via Zincke salt formation with the overall 35% yield and 84% N isotopic purity. Hyperpolarization studies of Signal Amplification by Reversible Exchange (SABRE) and SABRE in SHield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH) were performed to investigate the mechanism of polarization transfer from parahydrogen-derived hydride protons to F nucleus in milli-Tesla and micro-Tesla magnetic field regimes in N-3-F-pyridine and N-3-F-pyridine. We found the mismatch between N and F magnetic field hyperpolarization profiles in the micro-Tesla regime indicating that the spontaneous hyperpolarization process likely happens directly from parahydrogen-derived hydride protons to F nucleus without spin-relaying via N site.

N Hyperpolarization of Dalfampridine at Natural Abundance for Magnetic Resonance Imaging.

Signal Amplification by Reversible Exchange (SABRE) is a promising method for NMR signal enhancement and production of hyperpolarized molecules. As nuclear spin relaxation times of heteronuclei are usually much longer than those of protons, SABRE-based hyperpolarization of heteronuclei in molecules is highly important in the context of biomedical applications. In this work, we demonstrate that the SLIC-SABRE technique can be successfully used to hyperpolarize N nuclei in dalfampridine.

N MRI of SLIC-SABRE Hyperpolarized N-Labelled Pyridine and Nicotinamide.

Magnetic Resonance Imaging (MRI) is a powerful non-invasive diagnostic method extensively used in biomedical studies. A significant limitation of MRI is its relatively low signal-to-noise ratio, which can be increased by hyperpolarizing nuclear spins. One promising method is Signal Amplification By Reversible Exchange (SABRE), which employs parahydrogen as a source of hyperpolarization.

Chemical Exchange Reaction Effect on Polarization Transfer Efficiency in SLIC-SABRE.

Signal Amplification By Reversible Exchange (SABRE) is a new and rapidly developing hyperpolarization technique. The recent discovery of Spin-Lock Induced Crossing SABRE (SLIC-SABRE) showed that high field hyperpolarization transfer techniques developed so far were optimized for singlet spin order that does not coincide with the experimentally produced spin state. Here, we investigated the SLIC-SABRE approach and the most advanced quantitative theoretical SABRE model to date.