摘要
通过"点击化学"方法尝试埃罗替尼(Erlotinib)的^(18)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-^(18)F-氟叠氮乙烷(^(18)F-FEA)为放射化学反应中间体,通过"点击化学"反应制备^(18)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。^(18)F-FEA-Erlotinib自动化合成时间70 min,总放射化学产率为(54±2)%(n>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),K2.2.2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^(18)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^(18)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。
[Background] PET imaging of 11C-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 rain） of carbon-ll 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 rain） labeled Erlotinib. [Purpose] We automatically labelled Erlotinib with flurorine-18 through the ＂click chemistry＂ and explored its preliminary evaluation. [Methods] 18F-FEA-Erlotinib was synthesized from 2-18F-fluorine azide ethane （18F-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 18F-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. [ResultsJ XSF-FEA-Erlotinib was achieved within 70 min with （54±2）% radiochemical yield （decay corrected）, an average specific activity over 200 MBq＇lxrno1-1, and over 99% radiochemical purity. The logP of lSF-FEA-Erlofinib was 2.36±0.01. The final injection was free of bacteria and pyrogen, and the K2.2.2 concentration was lower than 10 mg.L-1. [Conclusion] lSF-FEA-Erlotinib was easy to be prepared by the ＂click chemistry＂ in an automatic synthesis system. 18F-FEA-Erlotinib has a similar lipophilicity to Erlotinib and a high metabolic stability in vitro.
出处
《核技术》
CAS
CSCD
北大核心
2018年第1期20-26,共7页
Nuclear Techniques
基金
广东省领军人才项目(2011)
广东省科技计划(No.2014A020212175)
广东省医学科研基金(No.A2015525)
南方医科大学2014科研启动计划(No.PY2014N048)
南方医院院长基金(No.2015C004)资助~~
