诊疗一体化探针 64Cu-DOTA-TATE的制备、 质量控制及分子影像

doi:10.7503/cjcu20170520

高等学校化学学报 ›› 2018, Vol. 39 ›› Issue (4): 695.doi: 10.7503/cjcu20170520

诊疗一体化探针 ⁶⁴Cu-DOTA-TATE的制备、质量控制及分子影像

刘菲, 谢卿, 刘特立, 徐晓霞, 郭晓轶, 李囡, 朱华(), 杨志()

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:2017-07-31 出版日期:2018-04-10 发布日期:2018-01-15
作者简介:联系人简介: 杨志, 男, 博士, 研究员, 博士生导师, 主要从事放射性药物研究. E-mail:pekyz@163.com;朱华, 男, 博士, 副研究员, 主要从事放射性药物研究. E-mail:zhuhuananjing@163.com
基金资助:
北京市科技新星项目(批准号: Z171100001117020)、国家自然科学基金(批准号: 81371592, 81401467)、北京市自然科学基金(批准号: 7162041)和北京市卫生局基金“215”学科骨干项目(批准号: 2015-3-072)资助

Radio-synthesis, Quality Control and Micro-PET Imaging of ⁶⁴Cu-DOTA-TATE^†

LIU Fei, XIE Qing, LIU Teli, XU Xiaoxia, GUO Xiaoyi, LI Nan, ZHU Hua^*(), YANG Zhi^*()

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing),Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China

Received:2017-07-31 Online:2018-04-10 Published:2018-01-15
Contact: ZHU Hua,YANG Zhi E-mail:zhuhuananjing@163.com;pekyz@163.com
Supported by:
† Supported by the 2017 Beijing Nova Program, China(No.Z171100001117020), the National Natural Science Foundation of China(Nos.81371592, 81401467), the Natural Science Foundation of Beijing, China(No.7162041) and the Beijing Municipal Commission of Health and Family Planning “215 Backbone Program”, China(No.2015-3-072)

摘要/Abstract

摘要：

采用放射性核素⁶⁴Cu标记生长抑素类似物DOTA-3-酪氨酰基-奥曲肽(DOTA-TATE), 制备了生长抑素受体显像分子探针⁶⁴Cu-DOTA-TATE; 分别测试了其在5%(体积分数)的人血清白蛋白(HSA)和0.9%(体积分数)生理盐水中的稳定性. 将⁶⁴Cu-DOTA-TATE经尾静脉注射入荷胰腺癌细胞裸鼠体内, 并分别于注射后1, 4和10 h进行小动物正电子发射断层(Micro-PET)显像. 结果表明, 经固相萃取小柱(Sep-Pak)分离纯化后, ⁶⁴Cu-DOTA-TATE的放射化学纯度>99%, 且40 h内在5%HSA和0.9%生理盐水中有良好的稳定性. Micro-PET显像结果表明, 随着时间延长, 肿瘤区域对⁶⁴Cu-DOTA-TATE放射性摄取增加.⁶⁴Cu-DOTA-TATE有望成为较好的生长抑素类似物的PET显像剂.

关键词: 生长抑素, 64Cu-DOTA-3-酪氨酰基-奥曲肽, 质量控制, 神经内分泌肿瘤

Abstract:

To investigate the potential of ⁶⁴Cu labeled DOTA-[Tyr3]-octreotate(DOTA-TATE) molecular probe in detecting somatostatin receptor(SSTR) positive tumors. The somatostatin analogue DOTA-TATE was radiolabeled with ⁶⁴Cu to prepare ⁶⁴Cu-DOTA-TATE. The stability of the probe was measured in 5%(volume ratio) HSA and 0.9%(volume ratio) saline solutions. After purification, 18.5 MBq of ⁶⁴Cu-DOTA-TATE was injected intravenously to nude mice bearing human pancreatic cancer via tail vein, micro-PET images were taken after radiotracer injection 1 and 10 h. After purification with 80%(volume ratio) ethanol, the radiochemical purity of ⁶⁴Cu-DOTA-TATE was over 99%, and could keep stable for 40 h in 5% HSA and 0.9% saline solutions. As shown in micro-PET imaging, tumor uptake was visualized after post injection 1 h, with the uptake increased after 10 h. ⁶⁴Cu-DOTA-TATE may be useful for imaging somatostatin receptor-positive tumors.

Key words: Somatostatin, 64Cu-DOTA-[Tyr3]-octreotate, Quality control, Neuroendocrine neoplasm

中图分类号:

O629.72
O615

TrendMD:

刘菲, 谢卿, 刘特立, 徐晓霞, 郭晓轶, 李囡, 朱华, 杨志. 诊疗一体化探针 ⁶⁴Cu-DOTA-TATE的制备、质量控制及分子影像. 高等学校化学学报, 2018, 39(4): 695.

LIU Fei, XIE Qing, LIU Teli, XU Xiaoxia, GUO Xiaoyi, LI Nan, ZHU Hua, YANG Zhi. Radio-synthesis, Quality Control and Micro-PET Imaging of ⁶⁴Cu-DOTA-TATE^†. Chem. J. Chinese Universities, 2018, 39(4): 695.

图/表 6

Scheme 1 Radiosynthesis of 64Cu-DOTA-TATE

Fig.1 MOLDI-TOF MS spectra of 64Cu-DOTA-TATE

Fig.2 In vitro stability of 64Cu-DOTA-TATE in 5% HSA(a) and 0.9% NaCl(b) solutions

Fig.3 Blood activity-time profile of 64Cu-DOTA-TATEThe profile of the curve was fitted to a two-compartment model.

Fig.4 Biodistribution of 64Cu-DOTA-TATE in percentage of injected dose per gram of organs after post-injection 1, 4 and 24 h in micea. Blood; b. heart; c. liver; d. spleen; e. kidneys; f. stomach; g. small intestine; h. large intestime; i. muscle; j. brain. Values are mean±standard deviation(n=3).

Fig.5 Micro-PET images of 64Cu-DOTA-TATE in nude mice bearing PANC-1 tumors after post-injection 1, 4 and 10 h(A) and corresponding SUV ratios of tumor to blood and muscle(B)(A) White arrows indicate the tumors. (B) a. SUV(T)/SUV(B); b. SUV(T)/SUV(M).

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诊疗一体化探针 ⁶⁴Cu-DOTA-TATE的制备、质量控制及分子影像

Radio-synthesis, Quality Control and Micro-PET Imaging of ⁶⁴Cu-DOTA-TATE^†

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