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

[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 fluorine-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 200 MBq · 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. (authors)