表皮生长因子受体显像剂18F-FEA-Erlotinib的自动化合成

摘要

通过"点击化学"方法尝试埃罗替尼(Erlotinib)的18F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2-18F-氟叠氮乙烷(18F-FEA)为放射化学反应中间体,通过"点击化学"反应制备18F-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.18F-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18F-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18F-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 of11C-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]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 of18F-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]18F-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 logP of18F-FEA-Erlotinib 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]18F-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.