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.

中文翻译：

---

利用仲氢可逆交换相分离信号放大甲硝唑抗生素在水介质中的 15N 超极化


甲硝唑是一种前瞻性超极化 MRI 造影剂，具有潜在的缺氧传感用途，可用于癌症、中风、神经退行性疾病等。我们展示了生产 ∼30 mM 超极化 [ ¹⁵ N ₃ N 位点上实现了超过 2.2% 的氮 15 极化。据报道， ¹⁵ NO ₂ 组在 1.4 T 的临床相关场中的 ¹⁵ N 极化 T ₁ 约为 12 分钟在水相中，表明超极化状态的寿命非常长。所产生的 [ ¹⁵ N ₃ ]甲硝唑水溶液仅含有约 100 μM 的残留 Ir，通过使用人胚胎细胞评估细胞代谢活性的 MTT 比色测试进行验证，认为具有生物相容性。肾HEK293T细胞。这种低成本和超快的超极化过程代表了用于 MRI 传感应用的生物相容性 HP [ ¹⁵ N ₃ ]甲硝唑（以及可能的其他超极化药物）制剂生产的重大进步。