研究论文

新型PET 核素68Ga 标记D-脱氧葡萄糖的合成及生物学评价

  • 杨志 ,
  • 朱华
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  • 北京大学肿瘤医院暨北京市肿瘤防治研究所 核医学科 恶性肿瘤发病机制及转化研究教育部重点实验室 北京 100142

收稿日期: 2011-12-27

  修回日期: 2012-02-27

  网络出版日期: 2012-05-18

基金资助

国家自然科学基金(Nos. 81071198, 81172082)资助项目.

Synthesis and Evaluation of New Nuclides Ga-68 Labeled D-Glucose for Potential PET Imaging Agent

  • YANG Zhi ,
  • ZHU Hua
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  • Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142

Received date: 2011-12-27

  Revised date: 2012-02-27

  Online published: 2012-05-18

Supported by

Project supported by the National Natural Science Foundation of China (Nos. 81071198, 81172082).

摘要

以2-氨基-2-脱氧-D-葡萄糖为原料, 通过微波加热法合成得到可用于核素标记的葡萄糖胺-1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸(DOTA)前体化合物. 产物通过IR, 1H NMR, HPLC-MS, ESI-HRMS 表征. 通过标记条件的优化设计, 在微波作用下, 与新型正电子显像核素Ga-68 进行放射性标记, 高产率得到68Ga-DOTA-DG. 而后对该标记化合物进行了K-562, Hela, A431 等肿瘤细胞摄取实验, 测定了对肿瘤的特异性. 68Ga-DOTA-DG 的合成, 拓宽了以18F-FDG 为首的肿瘤代谢类显像剂的新应用, 为PET (Positron emission tomography)显像肿瘤代谢情况提供了一种新的途径.

本文引用格式

杨志 , 朱华 . 新型PET 核素68Ga 标记D-脱氧葡萄糖的合成及生物学评价[J]. 化学学报, 2012 , 70(9) : 1066 -1072 . DOI: 10.6023/A1112275

Abstract

Starting from D-glucosamine (DG), the precursor compound 2-(4-isothiocyanatobenzyl)- 1,4,7,10-tetraazacyclo-dodecane-1,4,7,10-tetraacetic acid-D-glucose (DG-DOTA) was synthesized for potential radioactive imaging agents. Its structure was characterized by infrared, 1H NMR, LC-MS and ESI-HRMS. 68Ga is a generator-produced nuclide and does not require cyclotron on site. By careful selection of radiolabeling conditions, 68Ga-DOTA-DG was synthesized in short time and high yield by microwave synthesis system. Then, its binding affinity was tested by K-562, Hela and A431 tumor cell lines. The synthesis and evaluation of 68Ga-labeled DOTA-DG, not only provides a useful assessment of the stage of cancer by imaging tumor metabolites compared with 18F-FDG, but also develops a PET imaging agent.

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