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 [15N3]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 15N sites of [15N3]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 P15N of 3.2 %) by 15N−15N spin-relayed SABRE-SHEATH hyperpolarization technique, relying on simultaneous exchange of [15N3]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.
Original language | English |
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Pages (from-to) | 2406-2413 |
Number of pages | 8 |
Journal | Angewandte Chemie - International Edition |
Volume | 60 |
Issue number | 5 |
Early online date | 15 Oct 2020 |
DOIs | |
Publication status | Published - 1 Feb 2021 |
Keywords
- hyperpolarization
- nimorazole
- parahydrogen
- radiosensitization
- SABRE-SHEATH
- PARA-HYDROGEN
- HEAD
- PRODRUG EVOFOSFAMIDE TH-302
- HYPOXIA
- NECK-CANCER
- SIGNAL AMPLIFICATION
- INDUCED POLARIZATION
- SABRE
- METRONIDAZOLE
- PET
OECD FOS+WOS
- 1.04 CHEMICAL SCIENCES