Development of Dissolution Dynamic Nuclear Polarization of [15N3]Metronidazole: A Clinically Approved Antibiotic

David O. Guarin*, Sameer M. Joshi, Anna Samoilenko, Mohammad S.H. Kabir, Erin E. Hardy, Atsush M. Takahashi, Jan H. Ardenkjaer-Larsen, Eduard Y. Chekmenev, Yi Fen Yen*

*Corresponding author for this work

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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 using 15N 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 T1 values up to 343 s and 15N 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 the 15NO2 peak. The signal lasted over 13 min with notably long T2 of 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 HP 15N signals persisted over 70 s, demonstrating an unprecedented opportunity for in vivo studies.

Original languageEnglish
Article numbere202219181
JournalAngewandte Chemie - International Edition
Volume62
Issue number31
Number of pages6
ISSN1433-7851
DOIs
Publication statusPublished - 2023

Keywords

  • Dissolution-DNP
  • Hyperpolarization
  • Imaging Agents
  • Nitrogen-15
  • NMR Spectroscopy

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