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

We report dissolution Dynamic Nuclear Polarization (d-DNP) of [N-15(3)]metronidazole ([N-15(3)]MNZ) for the first time. Metronidazole is a clinically approved antibiotic, which can be potentially employed as a hypoxia-sensing molecular probe using N-15 hyperpolarized (HP) nucleus. The DNP process is very efficient for [N-15(3)]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 [N-15(3)]MNZ lasted remarkably long with T-1 values up to 343 s and N-15 polarizations up to 6.4 %. A time series of HP [N-15(3)]MNZ images was acquired in vitro using a steady state free precession sequence on the (NO2)-N-15 peak. The signal lasted over 13 min with notably long T-2 of 20.5 s. HP [N-15(3)]MNZ was injected in the tail vein of a healthy rat, and dynamic spectroscopy was performed over the rat brain. The in vivo HP N-15 signals persisted over 70 s, demonstrating an unprecedented opportunity for in vivo studies.