TY - JOUR

T1 - 15N NMR Signal Amplification by Reversible Exchange of [15N3]Ornidazole Antibiotic

AU - Yi, Anna P

AU - Chukanov, Nikita V

AU - Kabir, Mohammad S H

AU - Trepakova, Alexandra I

AU - Chekmenev, Eduard Y

AU - Salnikov, Oleg G

AU - Koptyug, Igor V

N1 - A.P.Y., N.V.C., and O.G.S. thank the Russian Science Foundation (grant 24-73-10093) for supporting SABRE hyperpolarization studies and [15N3]ornidazole synthesis. The ITC SB RAS team thanks the Ministry of Science and Higher Education of the Russian Federation for access to NMR equipment. E.Y.C. acknowledges NSF CHE-2404388, NIBIB R01 EB034197, and R21 EB033872.

PY - 2025/11/6

Y1 - 2025/11/6

N2 - Hyperpolarization techniques provide a dramatic enhancement of the sensitivity of magnetic resonance spectroscopy and imaging. Signal amplification by reversible exchange in shield enables alignment transfer to heteronuclei (SABRE-SHEATH) is an efficient technique for hyperpolarization of 13C and 15N nuclei in various biologically relevant compounds. Nitroimidazole antibiotics are prone to reduction under anaerobic conditions, making them prospective molecular contrast agents for the visualization of hypoxic tumors. In this work, we systematically studied 15N SABRE-SHEATH hyperpolarization of the ornidazole antibiotic at natural abundance (n.a.) of the 15N isotope and in the isotopically 15N3-labeled form. Optimization of such experimental conditions as polarization transfer magnetic field, temperature, parahydrogen pressure, and flow rate resulted in average 15N polarization levels of 9.3 ± 0.5% for n.a. ornidazole and 5.3 ± 0.2% for [15N3]ornidazole. T1 polarization decay time of 7.4 min was achieved for the 15NO2 group of [15N3]ornidazole at a clinically relevant 1.4 T magnetic field, allowing for the detection of the 15N NMR signal more than 20 min after hyperpolarization. DFT calculations of 15N chemical shifts for ornidazole and plausible intermediates and products of its reduction under hypoxic conditions showed that it should be feasible to discriminate these compounds by using 15N NMR.

AB - Hyperpolarization techniques provide a dramatic enhancement of the sensitivity of magnetic resonance spectroscopy and imaging. Signal amplification by reversible exchange in shield enables alignment transfer to heteronuclei (SABRE-SHEATH) is an efficient technique for hyperpolarization of 13C and 15N nuclei in various biologically relevant compounds. Nitroimidazole antibiotics are prone to reduction under anaerobic conditions, making them prospective molecular contrast agents for the visualization of hypoxic tumors. In this work, we systematically studied 15N SABRE-SHEATH hyperpolarization of the ornidazole antibiotic at natural abundance (n.a.) of the 15N isotope and in the isotopically 15N3-labeled form. Optimization of such experimental conditions as polarization transfer magnetic field, temperature, parahydrogen pressure, and flow rate resulted in average 15N polarization levels of 9.3 ± 0.5% for n.a. ornidazole and 5.3 ± 0.2% for [15N3]ornidazole. T1 polarization decay time of 7.4 min was achieved for the 15NO2 group of [15N3]ornidazole at a clinically relevant 1.4 T magnetic field, allowing for the detection of the 15N NMR signal more than 20 min after hyperpolarization. DFT calculations of 15N chemical shifts for ornidazole and plausible intermediates and products of its reduction under hypoxic conditions showed that it should be feasible to discriminate these compounds by using 15N NMR.

KW - Nitrogen Isotopes/chemistry

KW - Ornidazole/chemistry

KW - Anti-Bacterial Agents/chemistry

KW - Magnetic Resonance Spectroscopy

U2 - 10.1021/acs.jpcb.5c05057

DO - 10.1021/acs.jpcb.5c05057

M3 - Article

C2 - 41139910

VL - 129

SP - 11548

EP - 11556

JO - Journal of Physical Chemistry B

JF - Journal of Physical Chemistry B

SN - 1520-6106

IS - 44

ER -