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

We report dissolution Dynamic Nuclear Polarization (d-DNP) of [15 N3 ]metronidazole ([15 N3 ]MNZ) for the first time. Metronidazole is a clinically approved antibiotic, which can be potentially employed as a hypoxia-sensing molecular probe using 15 N hyperpolarized (HP) nucleus. The DNP process is very efficient for [15 N3 ]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 [15 N3 ]MNZ lasted remarkably long with T1 values up to 343 s and 15 N polarizations up to 6.4 %. A time series of HP [15 N3 ]MNZ images was acquired in vitro using a steady state free precession sequence on the 15 NO2 peak. The signal lasted over 13 min with notably long T2 of 20.5 s. HP [15 N3 ]MNZ was injected in the tail vein of a healthy rat, and dynamic spectroscopy was performed over the rat brain. The in vivo HP 15 N signals persisted over 70 s, demonstrating an unprecedented opportunity for in vivo studies.