TY - JOUR

T1 - 15N Hyperpolarization of Metronidazole Antibiotic in Aqueous Media Using Phase-Separated Signal Amplification by Reversible Exchange with Parahydrogen

AU - Sviyazov, Sergey V.

AU - Burueva, Dudari B.

AU - Chukanov, Nikita V.

AU - Razumov, Ivan A.

AU - Chekmenev, Eduard Y.

AU - Salnikov, Oleg G.

AU - Koptyug, Igor V.

N1 - S.V.S., D.B.B., N.V.C., I.A.R., and O.G.S. thank the Russian Science Foundation (grant 21-73-10105) for the support of conducting both CASH-SABRE and cytotoxicity experiments. E.Y.C. thanks NIH R21EB033872 and National Science Foundation grant (NSF) CHE-1904780. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank Gennadiy A. Kostin from Nikolaev Institute of Inorganic Chemistry SB RAS for help with the ICP-AES analysis.

PY - 2024/5/23

Y1 - 2024/5/23

N2 - 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 [15N3]metronidazole in aqueous media by using a phase-separated SABRE-SHEATH hyperpolarization method, with nitrogen-15 polarization exceeding 2.2% on all three 15N sites achieved in less than 2 min. The 15N polarization T1 of ∼12 min is reported for the 15NO2 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 [15N3]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 [15N3]metronidazole (and potentially other hyperpolarized drugs) formulation for MRI sensing applications.

AB - 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 [15N3]metronidazole in aqueous media by using a phase-separated SABRE-SHEATH hyperpolarization method, with nitrogen-15 polarization exceeding 2.2% on all three 15N sites achieved in less than 2 min. The 15N polarization T1 of ∼12 min is reported for the 15NO2 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 [15N3]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 [15N3]metronidazole (and potentially other hyperpolarized drugs) formulation for MRI sensing applications.

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85193078647&origin=inward&txGid=7d3d5f48dec816f55c9ef80e20ce5377

UR - https://www.mendeley.com/catalogue/aadaad87-3ae4-3cb7-bf42-8de155949773/

U2 - 10.1021/acs.jpclett.4c00875

DO - 10.1021/acs.jpclett.4c00875

M3 - Article

C2 - 38738984

VL - 15

SP - 5382

EP - 5389

JO - Journal of Physical Chemistry Letters

JF - Journal of Physical Chemistry Letters

SN - 1948-7185

IS - 20

ER -