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

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

Journal

Angewandte Chemie - International Edition
ISSN: 1433-7851

Output data

Year: 2020, Volume: 60, Number: 5, Pages: 2406-2413 Pages count : 8 DOI: 10.1002/anie.202011698

Authors

Salnikov Oleg G. ^1,2,3 , Chukanov Nikita V. ^1,2 , Svyatova Alexandra ^1,2 , Trofimov Ivan A. ^1,2 , Kabir Mohammad S.H. ⁴ , Gelovani Juri G. ^4,5 , Kovtunov Kirill V. ^1,2 , Koptyug Igor V. ^1,2 , Chekmenev Eduard Y. ^4,6

Affiliations

1	International Tomography Center SB RAS 3A Institutskaya St. 630090 Novosibirsk Russia
2	Department of Natural Sciences Novosibirsk State University 2 Pirogova St. 630090 Novosibirsk Russia
3	Boreskov Institute of Catalysis SB RAS 5 Acad. Lavrentiev Pr. 630090 Novosibirsk Russia
4	Department of Chemistry Integrative Biosciences (Ibio) Karmanos Cancer Institute (KCI) Wayne State University Detroit MI 48202 USA
5	College of Medicine and Health Sciences United Arab Emirates University Al Ain United Arab Emirates
6	Russian Academy of Sciences (RAS), 14 Leninskiy Prospekt, 119991 Moscow, Russia

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.

Salnikov O.G. , Chukanov N.V. , Svyatova A. , Trofimov I.A. , Kabir M.S.H. , Gelovani J.G. , Kovtunov K.V. , Koptyug I.V. , Chekmenev E.Y.
15N NMR Hyperpolarization of Radiosensitizing Antibiotic Nimorazole by Reversible Parahydrogen Exchange in Microtesla Magnetic Fields
Angewandte Chemie - International Edition. 2020. V.60. N5. P.2406-2413. DOI: 10.1002/anie.202011698 WOS Scopus OpenAlex

Submitted:	Aug 26, 2020
Published online:	Oct 15, 2020
Published print:	Dec 1, 2020

≡ Web of science:	WOS:000594405000001
≡ Scopus:	2-s2.0-85097006619
≡ OpenAlex:	W3092877373