Abstract We report dissolution Dynamic Nuclear Polarization (d‐DNP) of [15N3]metronidazole ([15N3]MNZ) for the first time. Metronidazole is a clinically approved antibiotic, which can be potentially employed as a hypoxia‐sensing molecular probe using15N hyperpolarized (HP) nucleus. The DNP process is very efficient for [15N3]MNZ with an exponential build‐up constant of 13.8 min using trityl radical. After dissolution and sample transfer to a nearby 4.7 T Magnetic Resonance Imaging scanner, HP [15N3]MNZ lasted remarkably long with T1values up to 343 s and15N polarizations up to 6.4 %. A time series of HP [15N3]MNZ images was acquired in vitro using a steady state free precession sequence on the15NO2peak. The signal lasted over 13 min with notably long T2of 20.5 s. HP [15N3]MNZ was injected in the tail vein of a healthy rat, and dynamic spectroscopy was performed over the rat brain. The in vivo HP15N signals persisted over 70 s, demonstrating an unprecedented opportunity for in vivo studies.
more »
« less
This content will become publicly available on February 6, 2026
15 N SABRE-SHEATH and NMR/DFT Characterization of Amino-Metronidazole, a Metabolic Product of the Antibiotic and Prospective Hypoxia Contrast Agent Metronidazole
- Award ID(s):
- 2404387
- PAR ID:
- 10600385
- Publisher / Repository:
- ACS
- Date Published:
- Journal Name:
- The Journal of Physical Chemistry B
- Volume:
- 129
- Issue:
- 5
- ISSN:
- 1520-6106
- Page Range / eLocation ID:
- 1662 to 1669
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract 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 of15N 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‐d4is 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 average15N polarization of up to 7.2–7.4 % for both substrates. The highest15N polarizations were observed in methanol‐d4for [15N3]metronidazole and in ethanol for [15N3]nimorazole. At a clinically relevant magnetic field of 1.4 T the15N 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.more » « less
An official website of the United States government
