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

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 [N-15(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 N-15 sites of [N-15(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 N-15-N-15 spin-relayed SABRE-SHEATH hyperpolarization technique, relying on simultaneous exchange of [N-15(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.

Automated summary

Nimorazole, an imidazole-based antibiotic, is being tested in Phase 3 clinical trials in Europe for its potential use as a hypoxia radiosensitizer for head and neck cancers. Researchers have successfully created a long-lasting hyperpolarized state for three N-15 sites of [N-15(3)]nimorazole, showing promise for its application in next-generation MRI-LINAC systems. The study also demonstrates the potential for efficient hyperpolarization of a wide range of imidazole-based antibiotics and chemotherapeutics using a spin-relayed technique.