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

• Published in: Angewandte Chemie 2021-02, Vol.133 (5), p.2436-2443
• Main Authors: Salnikov, Oleg G., Chukanov, Nikita V., Svyatova, Alexandra, Trofimov, Ivan A., Kabir, Mohammad S. H., Gelovani, Juri G., Kovtunov, Kirill V., Koptyug, Igor V., Chekmenev, Eduard Y.
• Format: Article
• Language: English
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202011698

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 [ 15 N 3 ]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 15 N sites of [ 15 N 3 ]nimorazole with T 1 of up to ca. 6 minutes. The nuclear spin polarization was boosted by ca. 67000‐fold at 1.4 T (corresponding to P 15N of 3.2 %) by 15 N− 15 N spin‐relayed SABRE‐SHEATH hyperpolarization technique, relying on simultaneous exchange of [ 15 N 3 ]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.