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

Autor: Sviyazov SV; International Tomography Center SB RAS, 3A Institutskaya St., Novosibirsk 630090, Russia.; Novosibirsk State University, 2 Pirogova St., Novosibirsk 630090, Russia., Burueva DB; International Tomography Center SB RAS, 3A Institutskaya St., Novosibirsk 630090, Russia., Chukanov NV; International Tomography Center SB RAS, 3A Institutskaya St., Novosibirsk 630090, Russia.; Novosibirsk State University, 2 Pirogova St., Novosibirsk 630090, Russia., Razumov IA; Novosibirsk State University, 2 Pirogova St., Novosibirsk 630090, Russia.; Institute of Cytology and Genetics SB RAS, 10 Lavrentiev Ave., Novosibirsk 630090, Russia., Chekmenev EY; Department of Chemistry, Integrative Bio-sciences (Ibio), Karmanos Cancer Institute (KCI), Wayne State University, Detroit, Michigan 48202, United States., Salnikov OG; International Tomography Center SB RAS, 3A Institutskaya St., Novosibirsk 630090, Russia., Koptyug IV; International Tomography Center SB RAS, 3A Institutskaya St., Novosibirsk 630090, Russia.
Jazyk: angličtina
Zdroj: The journal of physical chemistry letters [J Phys Chem Lett] 2024 May 23; Vol. 15 (20), pp. 5382-5389. Date of Electronic Publication: 2024 May 13.
DOI: 10.1021/acs.jpclett.4c00875
Abstrakt: 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 [ 15 N 3 ]metronidazole in aqueous media by using a phase-separated SABRE-SHEATH hyperpolarization method, with nitrogen-15 polarization exceeding 2.2% on all three 15 N sites achieved in less than 2 min. The 15 N polarization T 1 of ∼12 min is reported for the 15 NO 2 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 [ 15 N 3 ]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 [ 15 N 3 ]metronidazole (and potentially other hyperpolarized drugs) formulation for MRI sensing applications.
Databáze: MEDLINE