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

Oleg G. Salnikov; Nikita V. Chukanov; Alexandra Svyatova; Ivan A. Trofimov; Mohammad S.H. Kabir; Juri G. Gelovani; Kirill V. Kovtunov; Igor V. Koptyug; Eduard Y. Chekmenev

doi:10.1002/anie.202011698

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

Oleg G. Salnikov, Nikita V. Chukanov, Alexandra Svyatova, Ivan A. Trofimov, Mohammad S.H. Kabir, Juri G. Gelovani, Kirill V. Kovtunov, Igor V. Koptyug, Eduard Y. Chekmenev

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

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 P_15N 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
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	https://doi.org/10.1002/anie.202011698
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

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10.1002/anie.202011698

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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. (2021). ¹⁵N NMR Hyperpolarization of Radiosensitizing Antibiotic Nimorazole by Reversible Parahydrogen Exchange in Microtesla Magnetic Fields. Angewandte Chemie - International Edition, 60(5), 2406-2413. https://doi.org/10.1002/anie.202011698

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. / ¹⁵N NMR Hyperpolarization of Radiosensitizing Antibiotic Nimorazole by Reversible Parahydrogen Exchange in Microtesla Magnetic Fields. In: Angewandte Chemie - International Edition. 2021 ; Vol. 60, No. 5. pp. 2406-2413.

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title = "15N 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 [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.",

keywords = "hyperpolarization, nimorazole, parahydrogen, radiosensitization, SABRE-SHEATH, PARA-HYDROGEN, HEAD, PRODRUG EVOFOSFAMIDE TH-302, HYPOXIA, NECK-CANCER, SIGNAL AMPLIFICATION, INDUCED POLARIZATION, SABRE, METRONIDAZOLE, PET",

author = "Salnikov, {Oleg G.} and Chukanov, {Nikita V.} and Alexandra Svyatova and Trofimov, {Ivan A.} and Kabir, {Mohammad S.H.} and Gelovani, {Juri G.} and Kovtunov, {Kirill V.} and Koptyug, {Igor V.} and Chekmenev, {Eduard Y.}",

note = "Funding Information: O.G.S. thanks the Russian Foundation for Basic Research (Grant 19‐33‐60045) for the support of mechanistic studies with the use of parahydrogen. E.Y.C. thanks the following awards for funding support: NSF CHE‐1904780 and NIH 1R21CA220137. N.V.C., A.S., K.V.K. and I.V.K. thank the Russian Foundation for Basic Research (grants 17‐54‐33037, 18‐33‐20019 and 19‐53‐12013) for financial support and the Russian Ministry of Science and Higher Education (Project AAAA‐A16‐116121510087‐5). Publisher Copyright: {\textcopyright} 2020 Wiley-VCH GmbH Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = feb,

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doi = "10.1002/anie.202011698",

language = "English",

volume = "60",

pages = "2406--2413",

journal = "Angewandte Chemie - International Edition",

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Salnikov, OG , Chukanov, NV , Svyatova, A, Trofimov, IA, Kabir, MSH, Gelovani, JG, Kovtunov, KV, Koptyug, IV & Chekmenev, EY 2021, '¹⁵N NMR Hyperpolarization of Radiosensitizing Antibiotic Nimorazole by Reversible Parahydrogen Exchange in Microtesla Magnetic Fields', Angewandte Chemie - International Edition, vol. 60, no. 5, pp. 2406-2413. https://doi.org/10.1002/anie.202011698

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

In: Angewandte Chemie - International Edition, Vol. 60, No. 5, 01.02.2021, p. 2406-2413.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - 15N NMR Hyperpolarization of Radiosensitizing Antibiotic Nimorazole by Reversible Parahydrogen Exchange in Microtesla Magnetic Fields

AU - Salnikov, Oleg G.

AU - Chukanov, Nikita V.

AU - Svyatova, Alexandra

AU - Trofimov, Ivan A.

AU - Kabir, Mohammad S.H.

AU - Gelovani, Juri G.

AU - Kovtunov, Kirill V.

AU - Koptyug, Igor V.

AU - Chekmenev, Eduard Y.

N1 - Funding Information: O.G.S. thanks the Russian Foundation for Basic Research (Grant 19‐33‐60045) for the support of mechanistic studies with the use of parahydrogen. E.Y.C. thanks the following awards for funding support: NSF CHE‐1904780 and NIH 1R21CA220137. N.V.C., A.S., K.V.K. and I.V.K. thank the Russian Foundation for Basic Research (grants 17‐54‐33037, 18‐33‐20019 and 19‐53‐12013) for financial support and the Russian Ministry of Science and Higher Education (Project AAAA‐A16‐116121510087‐5). Publisher Copyright: © 2020 Wiley-VCH GmbH Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/2/1

Y1 - 2021/2/1

N2 - 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.

AB - 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.

KW - hyperpolarization

KW - nimorazole

KW - parahydrogen

KW - radiosensitization

KW - SABRE-SHEATH

KW - PARA-HYDROGEN

KW - HEAD

KW - PRODRUG EVOFOSFAMIDE TH-302

KW - HYPOXIA

KW - NECK-CANCER

KW - SIGNAL AMPLIFICATION

KW - INDUCED POLARIZATION

KW - SABRE

KW - METRONIDAZOLE

KW - PET

UR - http://www.scopus.com/inward/record.url?scp=85097006619&partnerID=8YFLogxK

U2 - 10.1002/anie.202011698

DO - 10.1002/anie.202011698

M3 - Article

C2 - 33063407

AN - SCOPUS:85097006619

VL - 60

SP - 2406

EP - 2413

JO - Angewandte Chemie - International Edition

JF - Angewandte Chemie - International Edition

SN - 1433-7851

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ER -