15 N Hyperpolarization of Metronidazole Antibiotic in Aqueous Media Using Phase-Separated Signal Amplification by Reversible Exchange with Parahydrogen
Metronidazole is a prospective hyperpolarized MRI contrast agent with potential hypoxia sensing utility for applications in cancer, stroke, neurodegenerative diseases, etc. We demonstrate a pilot procedure for production of ∼30 mM hyperpolarized [ N ]metronidazole in aqueous media by using a phase-s...
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Published in | The journal of physical chemistry letters Vol. 15; no. 20; pp. 5382 - 5389 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
23.05.2024
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Subjects | |
Online Access | Get full text |
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Summary: | Metronidazole is a prospective hyperpolarized MRI contrast agent with potential hypoxia sensing utility for applications in cancer, stroke, neurodegenerative diseases, etc. We demonstrate a pilot procedure for production of ∼30 mM hyperpolarized [
N
]metronidazole in aqueous media by using a phase-separated SABRE-SHEATH hyperpolarization method, with nitrogen-15 polarization exceeding 2.2% on all three
N sites achieved in less than 2 min. The
N polarization T
of ∼12 min is reported for the
NO
group at the clinically relevant field of 1.4 T in the aqueous phase, demonstrating a remarkably long lifetime of the hyperpolarized state. The produced aqueous solution of [
N
]metronidazole that contained only ∼100 μM of residual Ir was deemed biocompatible via validation through the MTT colorimetric test for assessing cell metabolic activity using human embryotic kidney HEK293T cells. This low-cost and ultrafast hyperpolarization procedure represents a major advance for the production of a biocompatible HP [
N
]metronidazole (and potentially other hyperpolarized drugs) formulation for MRI sensing applications. |
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ISSN: | 1948-7185 1948-7185 |
DOI: | 10.1021/acs.jpclett.4c00875 |