TY - JOUR

T1 - Solvent Effects in Hyperpolarization of 15N Nuclei in [15N3]Metronidazole and [15N3]Nimorazole Antibiotics via SABRE-SHEATH**

AU - Yi, Anna P.

AU - Salnikov, Oleg G.

AU - Burueva, Dudari B.

AU - Chukanov, Nikita V.

AU - Chekmenev, Eduard Y.

AU - Koptyug, Igor V.

N1 - A.P.Y., O.G.S., D.B.B. and N.V.C. thank the Russian ScienceFoundation (grant 21-73-10105). E.Y.C. thanks NSF CHE-1904780and NIBIB R21 EB033872.

PY - 2024/11

Y1 - 2024/11

N2 - Metronidazole and nimorazole are antibiotics of a nitroimidazole group which also may be potentially utilized as hypoxia radiosensitizers for the treatment of cancerous tumors. Hyperpolarization of 15N nuclei in these compounds using SABRE-SHEATH (Signal Amplification By Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei) approach provides dramatic enhancement of detection sensitivity of these analytes using magnetic resonance spectroscopy and imaging. Methanol-d4 is conventionally employed as a solvent in SABRE hyperpolarization process. Herein, we investigate SABRE-SHEATH hyperpolarization of isotopically labeled [15N3]metronidazole and [15N3]nimorazole in nondeuterated methanol and ethanol solvents. Optimization of such hyperpolarization parameters as polarization transfer magnetic field, temperature, parahydrogen flow rate and pressure allowed us to obtain an average 15N polarization of up to 7.2–7.4 % for both substrates. The highest 15N polarizations were observed in methanol-d4 for [15N3]metronidazole and in ethanol for [15N3]nimorazole. At a clinically relevant magnetic field of 1.4 T the 15N nuclei of these substrates possess long characteristic hyperpolarization lifetimes (T1) of ca. 1 to ca. 7 min. This study represents a major step toward SABRE in more biocompatible solvents, such as ethanol, and also paves the way for future utilization of these hyperpolarized nitroimidazoles as molecular contrast agents for MRI visualization of tumors.

AB - Metronidazole and nimorazole are antibiotics of a nitroimidazole group which also may be potentially utilized as hypoxia radiosensitizers for the treatment of cancerous tumors. Hyperpolarization of 15N nuclei in these compounds using SABRE-SHEATH (Signal Amplification By Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei) approach provides dramatic enhancement of detection sensitivity of these analytes using magnetic resonance spectroscopy and imaging. Methanol-d4 is conventionally employed as a solvent in SABRE hyperpolarization process. Herein, we investigate SABRE-SHEATH hyperpolarization of isotopically labeled [15N3]metronidazole and [15N3]nimorazole in nondeuterated methanol and ethanol solvents. Optimization of such hyperpolarization parameters as polarization transfer magnetic field, temperature, parahydrogen flow rate and pressure allowed us to obtain an average 15N polarization of up to 7.2–7.4 % for both substrates. The highest 15N polarizations were observed in methanol-d4 for [15N3]metronidazole and in ethanol for [15N3]nimorazole. At a clinically relevant magnetic field of 1.4 T the 15N nuclei of these substrates possess long characteristic hyperpolarization lifetimes (T1) of ca. 1 to ca. 7 min. This study represents a major step toward SABRE in more biocompatible solvents, such as ethanol, and also paves the way for future utilization of these hyperpolarized nitroimidazoles as molecular contrast agents for MRI visualization of tumors.

KW - NMR spectroscopy

KW - SABRE

KW - hyperpolarization

KW - nitroimidazoles

KW - parahydrogen

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85202678011&origin=inward&txGid=60e7595da1b4030fe87678a0fafb8ef4

UR - https://www.mendeley.com/catalogue/9f43ab72-0c14-3bb9-9a8a-f43ed6473c7b/

U2 - 10.1002/anse.202400045

DO - 10.1002/anse.202400045

M3 - Article

VL - 4

JO - Analysis and Sensing

JF - Analysis and Sensing

SN - 2629-2742

IS - 6

M1 - e202400045

ER -