表皮生长因子受体显像剂<sup>18</sup>F-FEA-Erlotinib的自动化合成

黄顺; 韩彦江; 胡孔珍; 王猛; 孙朋辉; 吴湖炳; 王全师; 赵肃清; 郑希

doi:10.11889/j.0253-3219.2018.hjs.41.010301

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表皮生长因子受体显像剂¹⁸F-FEA-Erlotinib的自动化合成

核化学、放射化学、放射性药物和核医学 | 更新时间：2021-05-19

- 表皮生长因子受体显像剂¹⁸F-FEA-Erlotinib的自动化合成
- Automated synthesis of EGFR imaging tracer ¹⁸F-FEA-Erlotinib
- 核技术 2018年41卷第1期文章编号：010301
- 作者机构：
  
  1.广东工业大学轻工化工学院广州 510006
  2.南方医科大学附属南方医院核医学科广州 510515
- 作者简介：
  
  [ "黄顺, 男, 1986年出生, 2012年毕业于广东工业大学, 现为博士研究生, 研究方向为正电子药物", "HUANG Shun, male, born in 1986, graduated from Guangdong University of Technology in 2012, doctoral student, focusing on the PET drugs" ]
  郑希, E-mail:xizheng@pharmacy.rutgers.edu ZHENG Xi, E-mail:xizheng@pharmacy.rutgers.edu
- 基金信息：
  
  广东省领军人才项目(2011);广东省科技计划(2014A020212175);广东省医学科研基金(A2015525);南方医科大学2014科研启动计划(PY2014N048);南方医院院长基金(2015C004)
- DOI：10.11889/j.0253-3219.2018.hjs.41.010301
  中图分类号： TL923
- 收稿日期：2017-07-26，
  
  修回日期：2017-09-26，
  
  纸质出版日期：2018-01-10
- 稿件说明：
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黄顺, 韩彦江, 胡孔珍, 等. 表皮生长因子受体显像剂¹⁸F-FEA-Erlotinib的自动化合成[J]. 核技术, 2018,41(1):010301

Shun HUANG, Yanjiang HAN, Kongzhen HU, et al. Automated synthesis of EGFR imaging tracer ¹⁸F-FEA-Erlotinib[J]. Nuclear techniques, 2018, 41(1): 010301
黄顺, 韩彦江, 胡孔珍, 等. 表皮生长因子受体显像剂¹⁸F-FEA-Erlotinib的自动化合成[J]. 核技术, 2018,41(1):010301 DOI： 10.11889/j.0253-3219.2018.hjs.41.010301.

Shun HUANG, Yanjiang HAN, Kongzhen HU, et al. Automated synthesis of EGFR imaging tracer ¹⁸F-FEA-Erlotinib[J]. Nuclear techniques, 2018, 41(1): 010301 DOI： 10.11889/j.0253-3219.2018.hjs.41.010301.

摘要

通过“点击化学”方法尝试埃罗替尼（Erlotinib）的

F标记，探索其全自动放化标记并进行初步评价。使用国产PET-MF-2V-IT-I合成模块，以2-

F-氟叠氮乙烷（

F-FEA）为放射化学反应中间体，通过“点击化学”反应制备

F-FEA-Erlotinib，产物经半制备高效液相色谱（High Performance Liquid Chromatography，HPLC）分离、C-18柱富集，最后经乙醇淋洗即得。

F-FEA-Erlotinib自动化合成时间70 min，总放射化学产率为（54±2）%（

5，衰变校正），放射化学纯度大于99%，放射性比活度高于200 MBq·μmol

-1

，K

2.2.2

含量低于10 mg·L

-1

，无菌无热原符合要求，体外稳定性好，具有和Erlotinib相似的亲脂性。自动化合成

F-FEA-Erlotinib操作简便，高效可靠，质量控制符合要求，能满足科研及临床用药要求，本工作为进一步研究

F-FEA-Erlotinib靶向表皮生长因子受体（Epithelial Growth Factor Receptor，EGFR）的肿瘤正电子断层扫描（Positron Emission Tomography，PET）显像奠定了良好基础。

Abstract

Background

PET imaging of

C-Erlotinib was used to distinguish responders from nonresponders in the targeted therapy for non-small cell lung cancer (NSCLC). However

the short half-life (20 min) of carbon-11 limits its widespread use as a tool for community-based diagnostic screening and therapeutic evaluation. We proposed that this shortcoming could be overcome by the development of a fluorine-18 (half-life is 109 min) labeled Erlotinib.

Purpose

We automatically labelled Erlotinib with flurorine-18 through the "click chemistry" and explored its preliminary evaluation.

Methods

F-FEA-Erlotinib was synthesized from 2-

F-fluorine azide ethane (

F-FEA)

a radiochemical intermediate

through the "click chemistry" in the PET-MF-2V-IT-I synthesis module and purified by semi-preparative high performance liquid chromatography (HPLC). The stability of

F-FEA-Erlotinib was performed in phosphate buffer saline (PBS) and fetal bovine serum (FBS). The octanol/water partition coefficient and routine quality control were tested.

Results

F-FEA-Erlotinib was achieved within 70 min with (54±2)% radiochemical yield (decay corrected)

an average specific activity over 200MBq·μmol

-1

and over 99% radiochemical purity. The log

F-FEA-Erlotinib was 2.36±0.01. The final injection was free of bacteria and pyrogen

and the K

2.2.2

concentration was lower than 10 mg·L

-1

Conclusion

F-FEA-Erlotinib was easy to be prepared by the "click chemistry" in an automatic synthesis system.

F-FEA-Erlotinib has a similar lipophilicity to Erlotinib and a high metabolic stability

in vitro

关键词

Keywords

references

R L Comis . The current situation: Erlotinib (Tarceva) and Gefitinib (Iressa) in non-small cell lung cancer . Oncologist , 2005 . 10 ( 7 ): 467 - 470 . DOI: 10.1634/theoncologist.10-7-467 http://doi.org/10.1634/theoncologist.10-7-467 .

B C Liao , C C Lin , J C Yang . Second and third-generation epidermal growth factor receptor tyrosine kinase inhibitors in advanced nonsmall cell lung cancer . Current Opinion in Oncology , 2015 . 27 ( 2 ): 94 - 101 . DOI: 10.1097/CCO.0000000000000164 http://doi.org/10.1097/CCO.0000000000000164 .

P Slobbe , A J Poot , A D Windhorst , . PET imaging with small-molecule tyrosine kinase inhibitors: TKI-PET . Drug Discovery Today , 2012 . 17 ( 21-22 ): 1175 - 1187 . DOI: 10.1016/j.drudis.2012.06.016 http://doi.org/10.1016/j.drudis.2012.06.016 .

J W Hicks , H F VanBrocklin , A A Wilson , . Radiolabeled small molecule protein kinase inhibitors for imaging with PET or SPECT . Molecules , 2010 . 15 ( 11 ): 8260 - 8278 . DOI: 10.3390/molecules15118260 http://doi.org/10.3390/molecules15118260 .

X Meng , BW Jr Loo , L Ma , . Molecular imaging with 11 C-PD153035 PET/CT predicts survival in non-small cell lung cancer treated with EGFR-TKI: a pilot study . Journal of Nuclear Medicine , 2011 . 52 ( 10 ): 1573 - 1579 . DOI: 10.2967/jnumed.111.092874 http://doi.org/10.2967/jnumed.111.092874 .

I Bahce , E F Smit , M Lubberink , . Development of [ 11 C]erlotinib positron emission tomography for in vivo evaluation of EGF receptor mutational status . Clinical Cancer Research , 2013 . 19 ( 1 ): 183 - 193 . DOI: 10.1158/1078-0432.CCR-12-0289 http://doi.org/10.1158/1078-0432.CCR-12-0289 .

A A Memon , S Jakobsen , F Dagnaes-Hansen , . Positron emission tomography (PET) imaging with [ 11 C]-labeled erlotinib: a micro-PET study on mice with lung tumor xenografts . Cancer Research , 2009 . 69 ( 3 ): 873 - 878 . DOI: 10.1158/0008-5472.CAN-08-3118 http://doi.org/10.1158/0008-5472.CAN-08-3118 .

A A Memon , B Weber , M Winterdahl , . PET imaging of patients with non-small cell lung cancer employing an EGF receptor targeting drug as tracer . British Journal of Cancer , 2011 . 105 ( 12 ): 1850 - 1855 . DOI: 10.1038/bjc.2011.493 http://doi.org/10.1038/bjc.2011.493 .

B Weber , M Winterdahl , A Memon , . Erlotinib accumulation in brain metastases from non-small cell lung cancer: visualization by positron emission tomography in a patient harboring a mutation in the epidermal growth factor receptor . Journal of Thoracic Oncology , 2011 . 6 ( 7 ): 1287 - 1289 . DOI: 10.1097/JTO.0b013e318219ab87 http://doi.org/10.1097/JTO.0b013e318219ab87 .

桂媛 , 徐志宏 , 张晓军 , . 细胞凋亡显像剂 18 F-ML-10前体合成及放射性标记 . 核化学与放射化学 , 2016 . 38 ( 3 ): 188 - 192 . DOI: 10.7538/hhx.2016.38.03.0188 http://doi.org/10.7538/hhx.2016.38.03.0188 .

Yuan GUI , Zhihong XU , Xiaojun ZHANG , . Synthesis precursor of apoptosis imaging agent 18 F-ML-10 and its radiolabing with 18 F . Journal of Nuclear and Radiochemistry , 2016 . 38 ( 3 ): 188 - 192 . DOI: 10.7538/hhx.2016.38.03.0188 http://doi.org/10.7538/hhx.2016.38.03.0188 .

国家药典委员会 . 中华人民共和国药典 , : 北京中国医药科技出版社 , 2015 . 1559 - 1660 .

Chinese Pharmacopoeia Commission . Pharmacopoeia of the People's Republic of China , : Beijing China's Medical Science and Technology Publishing House , 2015 . 1559 - 1660 .

T R Chan , R Hilgraf , K B Sharpless , . Polytriazoles as copper(Ⅰ)-stabilizing ligands in catalysis . Organic Letters , 2004 . 6 ( 17 ): 2853 - 2855 . DOI: 10.1021/ol0493094 http://doi.org/10.1021/ol0493094 .

贾丽娜 , 江大卫 , 程登峰 , . 一种靶向TGR5的胆汁酸类化合物的 18 F标记与初步评价 . 核化学与放射化学 , 2014 . 36 ( 4 ): 247 - 252 . DOI: 10.7538/hhx.YX.2014.2013076 http://doi.org/10.7538/hhx.YX.2014.2013076 .

Lina JIA , Dawei JIANG , Dengfeng CHENG , . Synthesis and preliminary evaluation of 18 F-labeled bile acid compound for TGR5 . Journal of Nuclear and Radiochemistry , 2014 . 36 ( 4 ): 247 - 252 . DOI: 10.7538/hhx.YX.2014.2013076 http://doi.org/10.7538/hhx.YX.2014.2013076 .

D H Truong , T H Tran , T Ramasamy , . Development of solid self-emulsifying formulation for improving the oral bioavailability of erlotinib . AAPS PharmSciTech , 2016 . 17 ( 2 ): 466 - 473 . DOI: 10.1208/s12249-015-0370-5 http://doi.org/10.1208/s12249-015-0370-5 .

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DOI：10.11889/j.0253-3219.2018.hjs.41.010301

摘要

Abstract

关键词

Keywords

references

表皮生长因子受体显像剂¹⁸F-FEA-Erlotinib的自动化合成

Automated synthesis of EGFR imaging tracer ¹⁸F-FEA-Erlotinib