Development of Dissolution Dynamic Nuclear Polarization of [<sup>15</sup>N<sub>3</sub>]Metronidazole: A Clinically Approved Antibiotic
David Guarin, Sameer M. Joshi, Anna Samoilenko, Mohammad Shah Hafez Kabir, Erin Hardy, Atsush M. Takahashi, Jan Henrik Ardenkjær‐Larsen, Eduard Y. Chekmenev, Yi‐Fen Yen
Abstract
Abstract We report dissolution Dynamic Nuclear Polarization (d‐DNP) of [ 15 N 3 ]metronidazole ([ 15 N 3 ]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 N 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 [ 15 N 3 ]MNZ lasted remarkably long with T 1 values up to 343 s and 15 N polarizations up to 6.4 %. A time series of HP [ 15 N 3 ]MNZ images was acquired in vitro using a steady state free precession sequence on the 15 NO 2 peak. The signal lasted over 13 min with notably long T 2 of 20.5 s. HP [ 15 N 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 15 N signals persisted over 70 s, demonstrating an unprecedented opportunity for in vivo studies.