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

Author:

Guarin David O.12ORCID,Joshi Sameer M.3,Samoilenko Anna3,Kabir Mohammad S. H.3,Hardy Erin E.1,Takahashi Atsush M.4,Ardenkjaer‐Larsen Jan H.25,Chekmenev Eduard Y.36ORCID,Yen Yi‐Fen1ORCID

Affiliation:

1. Department of Radiology Athinoula A. Martinos Center for Biomedical Imaging Massachusetts General Hospital 149 13th St. MA 02129 Charlestown USA

2. Polarize ApS. Asmussens Alle 1 1808 Frederiksberg Denmak

3. Department of Chemistry Integrative Biosciences (Ibio) Karmanos Cancer Institute (KCI) Wayne State University MI 48202 Detroit USA

4. Department of Brain and Cognitive Sciences McGovern Institute for Brain Research Massachusetts Institute of Technology MA 02139 Cambridge USA

5. Department of Health Technology Technical University of Denmark 348, Ørsteds Pl. 2800 Kongens Lyngby Denmark

6. Russian Academy of Sciences (RAS) 14 Leninskiy Prospekt 119991 Moscow Russia

Abstract

AbstractWe 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.

Funder

Division of Chemistry

Publisher

Wiley

Subject

General Medicine

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