Development of Dissolution Dynamic Nuclear Polarization of [(15) N(3) ]Metronidazole: A Clinically Approved Antibiotic

[(15)N(3)]甲硝唑(一种临床批准的抗生素)溶解动态核极化的研究进展

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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.

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