表皮生长因子受体显像剂¹⁸F-FEA-Erlotinib的自动化合成

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 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 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. 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 of ¹⁸F-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: 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.