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

ABSTRACT: 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 N₃ ]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 N₃ ]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 P_15N of 3.2 %) by ¹⁵ N-¹⁵ N spin-relayed SABRE-SHEATH hyperpolarization technique, relying on simultaneous exchange of [¹⁵ N₃ ]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.

SUBMITTER: Salnikov OG 

PROVIDER: S-EPMC7855180 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature