铁 (II) PARACEST 磁力共振成像对比剂
Sarina J Dorazio1, Pavel B Tsitovich, Kevin E Siters
1Department of Chemistry, University at Buffalo, State University of New York, Amherst, New York 14260, USA.
Journal of the American Chemical Society
|August 16, 2011
概括
第一个Fe(II) PARACEST药物使用宏环联体进行MRI对比. 这些偏磁化学交换和转移剂在低毫米度下显示可观测的CEST效应.
科学领域:
- 无机化学 无机化学
- 磁共振成像技术 磁共振成像技术
- 生物医学工程 生物医学工程
背景情况:
- 偏磁化学交换和转移 (PARACEST) 剂对于增强MRI灵敏度至关重要.
- 开发具有改进稳定性和明显化学转移的新型PARACEST剂是一个正在进行的研究领域.
- 铁 (II) 复合物具有作为成本效益高且可调节的 PARACEST 剂的潜力.
研究的目的:
- 报告了基于Fe (II) 的PARACEST磁共振对比剂的第一个例子.
- 为了合成和表征具有宏环配体 (L1和L2) 的新型铁 (II) 复合物.
- 评估这些新Fe (二) PARACEST剂的CEST特性和成像能力.
主要方法:
- 铁的合成 (II) 复合物与宏环 1,4,7-tris ((carbamoylmethyl) -1,4,7-triazacyclononane (L1) 和 1,4,7-tris[(5-amino-6-methyl-2-pyridyl) methyl]-1,4,7-triazacyclononane (L2) 的宏环联体.
- 在水溶液中确定Fe (II) 复合物的形成常数和稳定性.
- 用MRI描述可交换的质子及其CEST峰值位置.
- 在不同的度,pH值,离子强度和温度下,CEST对溶液进行成像实验.
主要成果:
- 合成了具有宏循环配体L1和L2的稳定Fe(II) 复合体,其形成常数分别为log K = 13.5和19.2.
- 复合物在空气存在时保持Fe (II) 状态.
- [Fe(L1) ](2+) 的氨基质子在69ppm的CEST峰值,而[Fe(L2) ](2+) 的氨基质子在6ppm的水下表现出峰值.
- 在生理条件下 (pH 7,100 mM NaCl,20 mM缓冲区,25 °C或37 °C) 的低毫米度下,可以观察到CEST效应.
结论:
- 基于宏循环配体的新型Fe (II) PARACEST剂已经成功开发出来.
- 这些药物表现出明显的CEST峰值转移,并且在相关的生理条件下可以观察到.
- 这些发现为MRI对比剂提供了有希望的新候选者,特别是基于Fe (II) 的PARACEST应用.
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