Automated synthesis of EGFR imaging tracer <sup>18</sup>F-FEA-Erlotinib

Shun HUANG; Yanjiang HAN; Kongzhen HU; Meng WANG; Penghui SUN; Hubing WU; Quanshi WANG; Suqing ZHAO; Xi ZHENG

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

您当前的位置：

首页 >

文章列表页 >

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

NUCLEAR CHEMISTRY, RADIOCHEMISTRY, RADIOPHARMACEUTICALS AND NUCLEAR MEDICINE | 更新时间：2021-05-19

- Automated synthesis of EGFR imaging tracer ¹⁸F-FEA-Erlotinib
- NUCLEAR TECHNIQUES Vol. 41, Issue 1, Article number: 010301(2018)
- 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：
- 基金信息：
  
  Guangdong Province Leadership;Science and Technology Program of Guangdong;Medical Research Foundation of Guangdong Province;Scientific Research Initiative of Southern Medical University;President's Fund of Nanfang Hospital
- DOI：10.11889/j.0253-3219.2018.hjs.41.010301
  CLC： TL923
- Received：26 July 2017，
  
  Revised：26 September 2017，
  
  Published：10 January 2018
- 稿件说明：
移动端阅览
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：

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 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Click synthesis of PET radiopharmaceuticals

Simple and rapid synthesis of tumor imaging agents¹⁸F-FAC and ¹⁸F- FMISO

Efficiently automated synthesis of 2-[¹⁸F]-fluoro-2-deoxy-D-glucose

Related Author

XU Mei KUANG Chunxiang

匡春香

TANG Ganghua TANG Xiaolan WANG Mingfang LUO Lei GAN Manquan

唐小兰

王明芳

罗磊

甘满权

TANG Ganghua1 TANG Xiaolan2 WANG Mingfang1 GUO Xiaojun1 1

Related Institution

Department of Chemistry Tongji University

PET Centre, Department of Nuclear Medicine, Nan Fang Hospital, Southern Medical University

华南农业大学理学院

PET Centre, Department of Nuclear Medicine, Nan Fang Hospital, Southern Medical University, Guangzhou 510515) 2

AI问答

Address：2019 Jialuo Road, Jiading, Shanghai, China Postal code：201800
Tel：021-39194977 Email：LHB@sinap.ac.cn
Technical support is provided by Beijing Founder electronics co., LTD 沪ICP备05005479号-1 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.
Total Visits：880473

⁰

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

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

摘要

Abstract

关键词

Keywords

references

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