15 N Hyperpolarization of Metronidazole Antibiotic in Aqueous Media Using Phase-Separated Signal Amplification by Reversible Exchange with Parahydrogen

• Published in: The journal of physical chemistry letters Vol. 15; no. 20; pp. 5382 - 5389
• Main Authors: Sviyazov, Sergey V, Burueva, Dudari B, Chukanov, Nikita V, Razumov, Ivan A, Chekmenev, Eduard Y, Salnikov, Oleg G, Koptyug, Igor V
• Format: Journal Article
• Language: English
• Published: United States 23.05.2024
• Subjects: Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Contrast Media - chemistry; HEK293 Cells; Humans; Hydrogen - chemistry; Magnetic Resonance Imaging - methods; Metronidazole - chemistry; Metronidazole - pharmacology; Nitrogen Isotopes - chemistry; Water - chemistry
• DOI: 10.1021/acs.jpclett.4c00875
• ISSN: 1948-7185

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.