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Parahydrogen-induced polarization of¹³C nuclei by side-arm hydrogenation (PHIP-SAH) for [1-¹³C]acetate and [1-¹³C]pyruvate esters with application of PH-INEPT-type pulse sequences for¹H to¹³C 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 in¹³C polarization values of 0.66 ± 0.04% and 0.19 ± 0.02% for allyl [1-¹³C]pyruvate and ethyl [1-¹³C]acetate, respectively, which is lower than the corresponding polarization levels obtained with MFC for¹H to¹³C polarization transfer (3.95 ± 0.05% and 0.65 ± 0.05% for allyl [1-¹³C]pyruvate and ethyl [1-¹³C]acetate, respectively). Nevertheless, a significant¹³C NMR signal enhancement with respect to thermal polarization allowed us to perform¹³C MR imaging of both biologically relevant hyperpolarized molecules which can be used to produce useful contrast agents for the in vivo imaging applications.

 

15 N spin–lattice relaxation dynamics in metronidazole- 15 N 3 and metronidazole- 15 N 2 isotopologues are studied for rational design of 15 N-enriched biomolecules for signal amplification by reversible exchange in microtesla fields. 15 N relaxation dynamics mapping reveals the deleterious effects of interactions with the polarization transfer catalyst and a quadrupolar 14 N nucleus within the spin-relayed 15 N– 15 N network. 

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 imagingin vivo. Several hyperpolarization techniques exist for hyperpolarization of a large repertoire of nuclear spins, although the¹³C and¹⁵N sites of biocompatible agents are the key targets due to their widespread use in biochemical pathways. Moreover, their longT₁allows hyperpolarized states to be retained for up to tens of minutes. Signal amplification by reversible exchange (SABRE) is a low‐cost and ultrafast hyperpolarization technique that has been shown to be versatile for the hyperpolarization of¹⁵N nuclei. Although large sensitivity gains are enabled by hyperpolarization,¹⁵N natural abundance is only ∼0.4 %, so isotopic labeling of the molecules to be hyperpolarized is required in order to take full advantage of the hyperpolarized state. Herein, we describe selected advances in the preparation of¹⁵N‐labeled compounds with the primary emphasis on using these compounds for SABRE polarization in microtesla magnetic fields through spontaneous polarization transfer from parahydrogen. Also, these principles can certainly be applied for hyperpolarization of these emerging contrast agents using dynamic nuclear polarization and other techniques.

 

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 [¹⁵N₃]nimorazole as a theragnostic hypoxia contrast agent that can be potentially deployed in the next‐generation MRI‐LINAC systems. Herein, we report the first steps to create long‐lasting (for tens of minutes) hyperpolarized state on three¹⁵N sites of [¹⁵N₃]nimorazole with T₁of up to ca. 6 minutes. The nuclear spin polarization was boosted by ca. 67000‐fold at 1.4 T (corresponding toP_15Nof 3.2 %) by¹⁵N−¹⁵N spin‐relayed SABRE‐SHEATH hyperpolarization technique, relying on simultaneous exchange of [¹⁵N₃]nimorazole and parahydrogen on polarization transfer Ir‐IMes catalyst. The presented results pave the way to efficient spin‐relayed SABRE‐SHEATH hyperpolarization of a wide range of imidazole‐based antibiotics and chemotherapeutics.

 

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 [¹⁵N₃]nimorazole as a theragnostic hypoxia contrast agent that can be potentially deployed in the next‐generation MRI‐LINAC systems. Herein, we report the first steps to create long‐lasting (for tens of minutes) hyperpolarized state on three¹⁵N sites of [¹⁵N₃]nimorazole with T₁of up to ca. 6 minutes. The nuclear spin polarization was boosted by ca. 67000‐fold at 1.4 T (corresponding toP_15Nof 3.2 %) by¹⁵N−¹⁵N spin‐relayed SABRE‐SHEATH hyperpolarization technique, relying on simultaneous exchange of [¹⁵N₃]nimorazole and parahydrogen on polarization transfer Ir‐IMes catalyst. The presented results pave the way to efficient spin‐relayed SABRE‐SHEATH hyperpolarization of a wide range of imidazole‐based antibiotics and chemotherapeutics.