波谱学杂志 ›› 2015, Vol. 32 ›› Issue (2): 273-282.doi: 10.11938/cjmr20150210

• 研究论文 • 上一篇    下一篇

一种肝脏类生物相容性氨基酸共聚物磁共振成像造影剂

肖研1,湛游洋1,薛蓉1,李晓晶1*,裴奉奎1,冯江华2*,占博涵2   

  1. 1. 中国科学院 长春应用化学研究所,长春 130022;
    2. 厦门大学 电子科学系,厦门 361005
  • 收稿日期:2015-01-30 修回日期:2015-05-19 出版日期:2015-06-05 发布日期:2015-06-05
  • 作者简介:*通讯联系人:李晓晶,电话:+86-431-85262219, E-mail: xjli@ciac.ac.cn; 冯江华,电话:+86-592-2183301, E-mail: jianghua.feng@xmu.edu.cn.
  • 基金资助:

    The National Natural Science Foundation of China (20975097 and 21305134).

A Biocompatible Gadolinium (III)-Poly (Aspartic Acid-Co-Phenylalanine) for Liver Magnetic Resonance Imaging Contrast Agent

XIAO Yan1,ZHAN You-yang1,XUE Rong1,LI Xiao-jing1*,PEI Feng-kui1,FENG Jiang-hua2*,ZHAN Bo-han2   

  1. 1. Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022;
    2. Department of Electronic Science, Xiamen University, Xiamen 361005
  • Received:2015-01-30 Revised:2015-05-19 Online:2015-06-05 Published:2015-06-05
  • About author:XIAO Yan(1984-), female, born in Hebei province, PhD., specializing in MRI contrast. *Corresponding author:LI Xiao-jing, Tel: +86-431-85262219, E-mail: xjli@ciac.ac.cn; FENG Jiang-hua, Tel: +86-592-2183301, E-mail: jianghua.feng@xmu.edu.cn.
  • Supported by:

    The National Natural Science Foundation of China (20975097 and 21305134).

摘要:

一种新型的以天门冬氨酸-苯丙氨酸共聚物为载体的大分子生物相容性材料(AP-EDA-DOTA-Gd)被制备出来作为磁共振成像造影剂.首先合成了天门冬氨酸-苯丙
氨酸共聚物,之后利用乙二胺将1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸(DOTA)连接到共聚物上,最后将钆离子通过配位的作用方式连接到DOTA 上,最终得到大分子AP-EDA-DOTA-Gd.体外溶血性试验表明AP-EDA-DOTA-Gd 具有较好的血液相容性.在pH = 5.5 的组织蛋白酶B 的磷酸缓冲液中,AP-EDA-DOTA-Gd 能够降解.APEDA-DOTA-Gd 的体外弛豫效率(15.95 mmol–1?L?s–1)为目前临床应用的Gd-DOTA (5.59mmol–1?L?s–1)的2.9 倍.大鼠肝脏成像实验结果表明,AP-EDA-DOTA-Gd 对于肝组织的成像增强对比度为63.5±6.1%远高于Gd-DOTA (24.2±2.9%).

关键词: MRI 造影剂, 钆大分子, 肝脏, 弛豫效率

Abstract:

A new biocompatible gadolinium (III)-macromolecule (AP-EDA-DOTA-Gd) was developed as a magnetic resonance imaging (MRI) contrast agent. Poly (aspartic acid-cophenylalanine) was synthesized, modified via ethylenediamine, conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and finally chelated gadolinium (III), yielding gadolinium (III)-based macromolecule (AP-EDA-DOTA-Gd). The hemolytic tests showed the hemocompatibility of this gadolinium (III)-based macromolecular conjugate. In vitro, AP-EDA-DOTA-Gd could be degraded, when it was incubated with cathepsin B in phosphate buffered solution (pH = 5.5). The T1-relaxivity (15.95 mmol–1·L·s–1) of AP-EDA-DOTA-Gd was 2.9 times of that (5.59 mmol–1·L·s–1) of the clinical MRI contrast agent (Gd-DOTA) at 1.5 T and 25 ℃. The liver enhancement of AP-EDA-DOTA-Gd was 63.5±6.1% during the maximum enhancement time (50-80 min), which was much better than that of Gd-DOTA (24.2±2.9%, 10-30 min). AP-EDA-DOTA-Gd was expected to be a potential liver MRI contrast agent.

Key words: MRI contrast agent, gadolinium (III)-macromolecule, liver, relaxivity

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