Development of Hyperpolarized 15N-labeled Metronidazole as an MR Contrast Agent by d-DNP Technique: A Potential Antibiotic and Hypoxia Probe
David Guarin Bedoya1,2, Erin Elizabeth Hardy1, Anna Samoilenko3, Sameer Joshi3, Jason Stockmann1, Jan Henrik Ardenkjaer-Larsen2,4, Matthew S. Rosen1,5,6, Boyd M. Goodson7, Thomas Theis8, Eduard Y Chekmenev3,9, and Yi-Fen Yen1
1Radiology Department, Athinoula A. Martinos Center for Biomedical Imaging, Massachusttes General Hospital, Boston, MA, United States, 2Polarize ApS, Frederiksberg, Denmark, 3Department of Chemistry, Wayne State University, Detroit, MI, United States, 4Department of Electrical Engineering, Technical University of Denmark, Kongens Lyngby, Denmark, 5Radiology Department, Harvard Medical School, Boston, MA, United States, 6Physics Department, Havard University, Boston, MA, United States, 7School of Chemical and Biomolecular Sciences, Southern Illinois University, Carbondale, IL, United States, 8Department of Chemistry, North Carolina State University, Raleigh, NC, United States, 9Russian Academy of Sciences, Moscow, Russian Federation
In this work, we developed a DNP hyperpolarized 15N-labeled metronidazole contrast agent. The formulation of the sample and the DNP process were optimized to reduce the build-up time constant down to 22 min while reaching liquid state signal enhancements of 104. The T1 relaxation times were measured in liquid-state, and found to be minutes long. Due to the high enhancement and long T1, MNZ hyperpolarized 15N signal could be monitored for several minutes. The contrast agent was tested with MRS in-vivo, in a rat brain. The hyperpolarized MNZ signal remained above the noise level for more than a minute.
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