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 three 15N sites of [15N3]nimorazole with T1 of up to ca. 6 minutes. The nuclear spin polarization was boosted by ca. 67000‐fold at 1.4 T (corresponding to P15N of 3.2 %) by 15N−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 three 15N sites of [15N3]nimorazole with T1 of up to ca. 6 minutes. The nuclear spin polarization was boosted by ca. 67000‐fold at 1.4 T (corresponding to P15N of 3.2 %) by 15N−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.

Signal Amplification by Reversible Exchange (SABRE) technique enables nuclear spin hyperpolarization of wide range of compounds using parahydrogen. Here we present the synthetic approach to prepare 15N‐labeled [15N]dalfampridine (4‐amino[15N]pyridine) utilized as a drug to reduce the symptoms of multiple sclerosis. The synthesized compound was hyperpolarized using SABRE at microtesla magnetic fields (SABRE‐SHEATH technique) with up to 2.0 % 15N polarization. The 7‐hour‐long activation of SABRE pre‐catalyst [Ir(IMes)(COD)Cl] in the presence of [15N]dalfampridine can be remedied by the use of pyridine co‐ligand for catalyst activation while retaining the 15N polarization levels of [15N]dalfampridine. The effects of experimental conditions such as polarization transfer magnetic field, temperature, concentration, parahydrogen flow rate and pressure on 15N polarization levels of free and equatorial catalyst‐bound [15N]dalfampridine were investigated. Moreover, we studied 15N polarization build‐up and decay at magnetic field of less than 0.04 μT as well as 15N polarization decay at the Earth's magnetic field and at 1.4 T.