Salnikov, Oleg G, Nikita V Chukanov, Alexandra Svyatova, Ivan A Trofimov, Mohammad S. H. Kabir, Juri G Gelovani, Kirill V Kovtunov, Igor V Koptyug, and Eduard Y Chekmenev. “15N NMR Hyperpolarization of Radiosensitizing Antibiotic Nimorazole via Reversible Parahydrogen Exchange in Microtesla Magnetic Fields.” Angewandte Chemie International Edition, October 15, 2020, anie.202011698.
https://doi.org/10.1002/anie.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 [15N3]nimorazole as a theragnostic hypoxia contrast agent that can be potentially deployed in the nextgeneration MRI-LINAC systems. Here, we report the first but very important steps to create long-lasting (for tens of minutes) hyperpolarized state on three 15N sites of [15N3]nimorazole with T1 of up to ~6 minutes. The nuclear spin polarization was boosted by ~67000-fold at 1.4 T (corresponding to P15N of 3.2%) via 15N-15N spin-relayed SABRE-SHEATH hyperpolarization technique relying on simultaneous exchange of [15N3]nimorazole and parahydrogen on polarization transfer Ir-IMes catalyst. The isomeric side product of [15N3]nimorazole synthesis was hyperpolarized too. The presented results pave the way to efficient spin-relayed SABRE-SHEATH hyperpolarization of a wide range of imidazole-based antibiotics and chemotherapeutics.