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15 N NMR Hyperpolarization of Radiosensitizing Antibiotic Nimorazole by Reversible Parahydrogen Exchange in Microtesla Magnetic Fields
Author(s) -
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.
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202011698
Subject(s) - hyperpolarization (physics) , spin isomers of hydrogen , imes , chemistry , nuclear magnetic resonance , radiosensitizer , induced polarization , nuclear magnetic resonance spectroscopy , physics , stereochemistry , medicine , hydrogen , carbene , radiation therapy , catalysis , biochemistry , organic chemistry , quantum mechanics , electrical resistivity and conductivity
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.