发展溶解动态核极化[15 N3]的Metronidazole:一个临床批准的抗生素
David O Guarin1,2, Sameer M Joshi3, Anna Samoilenko3
1Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, 149 13th St., MA 02129, Charlestown, USA.
Angewandte Chemie (International ed. in English)
|May 29, 2023
概括
我们为15N3-metronidazole实现了溶解动态核极化 (d-DNP),这是一个潜在的缺氧探针. 超极化15N3-metronidazole在体外和体内显示长时间的信号持久性,使新的成像研究成为可能.
科学领域:
- 核磁共振光谱学 核磁共振光谱学
- 医疗成像医学成像
- 生物医学工程 生物医学工程
背景情况:
- 甲尼达是一种抗生素,具有作为低氧感应探针的潜力.
- 动态核极化 (DNP) 增强了核自旋极化,提高了MRI灵敏度.
- 15N超极化 (HP) 核为分子成像提供独特的光谱特性.
研究的目的:
- 报告15N3-metronidazole (15N3-MNZ) 的第一个动态核极化 (d-DNP) 溶解.
- 评估使用HP 15N3-MNZ作为低氧感应分子探针的可行性.
- 在体外和体内评估HP 15N3-MNZ的信号持久性和成像能力.
主要方法:
- 溶解DNP在15N3-metronidazole上使用三基进行.
- 超极化15N3-MNZ被转移到4.7TMRI扫描仪进行成像.
- 在体外成像中使用了稳定状态自由先行序列.
- 在小鼠模型中,在静脉注射后进行了体内动态光谱学.
主要成果:
- 15N3-MNZ的高效DNP积累与一个13.8分钟的常量.
- 实现了长T1放松时间 (高达343秒) 和高15N极化 (高达6.4%).
- 试验室信号持续超过13分钟,T2为20.5秒.
- 在生体中,大鼠大脑中的HP 15N信号持续超过70秒.
结论:
- HP 15N3-MNZ可以使用d-DNP.成功制备.
- 长时间的信号持久性和体内检测能力为缺氧成像提供了机会.
- 这种技术展示了使用超极化剂的先进生物医学应用的潜力.
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