Development of Dissolution Dynamic Nuclear Polarization of [15N3]Metronidazole: a Clinical Approved Antibiotic.

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. 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 15NO2peak. 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.