靶向核磁造影剂Gd-DOTA-E-2的制备及性能研究

陶玉贵, 江志超, 葛飞, 朱龙宝, 吴文斌, 黄月玲, 宋平, 李婉珍

中国药学杂志 ›› 2018, Vol. 53 ›› Issue (18) : 1541-1546.

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中国药学杂志 ›› 2018, Vol. 53 ›› Issue (18) : 1541-1546. DOI: 10.11669/cpj.2018.18.003
论著

靶向核磁造影剂Gd-DOTA-E-2的制备及性能研究

  • 陶玉贵, 江志超, 葛飞, 朱龙宝, 吴文斌, 黄月玲, 宋平, 李婉珍
作者信息 +

Preparation and Performance Research of Target NMR Contrast Agent Gd-DOTA-E-2

  • TAO Yu-gui, JIANG Zhi-chao, GE Fei, ZHU Long-bao, WU Wen-bin, HUANG Yue-ling, SONG Ping, LI Wan-zhen
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摘要

目的 制备Gd-DOTA-E-2靶向造影剂,并对其弛豫性能、细胞毒性以及靶向性进行评价。方法 采用F-moc固相法合成靶向双环肽E-2,与螯合剂1,4,7,10-四氮环十二烷基-1,4,7,10-四乙酸(DOTA)共价连接,利用配位键螯合Gd3+,制备核磁共振成像(MRI)造影剂Gd-DOTA-E-2。并用质谱仪(ESI-MS)、核磁共振仪(NMR)对其结构进行表征,通过弛豫性能、四甲基偶氮唑蓝法(MTT)、小鼠MRI造影实验对其性能进行评价。结果 ESI-MS、NMR结果表明,Gd-DOTA-E-2合成成功,弛豫效率(k=9.551 mmol-1·L·s-1)是商用造影剂钆特酸葡胺注射液(Gd-DOTA)的1.84倍;MTT实验结果显示,Gd-DOTA-E-2的细胞毒性低于Gd-DOTA;小鼠MRI造影实验结果显示,Gd-DOTA-E-2具有靶向性并成像清晰。结论 Gd-DOTA-E-2是一种在生物体内稳定性好,细胞毒性低,并有靶向性能的MRI造影剂,具有研究和应用价值。

Abstract

OBJECTIVE To prepare Gd-DOTA-E-2 targeted contrast agent and evaluate its relaxation properties, cytotoxicity and targeting. METHODS E-2 was synthesized by F-moc solid phase method, covalently bonded with chelating agent DOTA, meanwhile ultilizing chelating ligand Gd3+ to prepare MRI contrast agent Gd-DOTA-E-2. The structure was characterized by ESI-MS and NMR, and the properties were evaluated by relaxation properties, MTT and mouse MRI contrast assay. RESULTS ESI-MS and NMR RESULTS showed that Gd-DOTA-E-2 was synthesized successfully, and its relaxation efficiency(k=9.551 mmol-1·L·s-1) is 1.84 times more efficient than a commercially available contrast agent of Gd-DOTA; MTT RESULTS showed that the toxicity of Gd-DOTA-E-2 cell is lower than that of Gd-DOTA; the experimental RESULTS in MRI angiography showed that Gd-DOTA-E-2 is possessing of targeting and can image clearly. CONCLUSION Gd-DOTA-E-2 is a kind of MRI contrast agent with good stability, low cytotoxicity and targeted properties in vivo,which is valuable in research and application.

关键词

E-2双环肽 / 固相合成 / 靶向 / MRI造影

Key words

E-2 double loop peptide / solid phase synthesis / targeting / MRI angiography

引用本文

导出引用
陶玉贵, 江志超, 葛飞, 朱龙宝, 吴文斌, 黄月玲, 宋平, 李婉珍. 靶向核磁造影剂Gd-DOTA-E-2的制备及性能研究[J]. 中国药学杂志, 2018, 53(18): 1541-1546 https://doi.org/10.11669/cpj.2018.18.003
TAO Yu-gui, JIANG Zhi-chao, GE Fei, ZHU Long-bao, WU Wen-bin, HUANG Yue-ling, SONG Ping, LI Wan-zhen. Preparation and Performance Research of Target NMR Contrast Agent Gd-DOTA-E-2[J]. Chinese Pharmaceutical Journal, 2018, 53(18): 1541-1546 https://doi.org/10.11669/cpj.2018.18.003
中图分类号: R981   

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基金

国家自然科学基金面上项目资助(31671797);安徽省重大科技专项资助(17030701014);安徽省高等学校省级自然科学研究重点项目资助(KJ2016A801、KJ2017A123);国家级大学生创新创业训练计划项目资助(2016103630056、2016103630062);安徽工程大学中青年拔尖人才项目资助(2016BJRRC006)
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