Custom-built automated radiosynthesis platform for Al[18F]F radiochemistry and its application for clinical production

The construction of fully automated Al[18F]F radiochemistry can enhance the reproducibility and reliability of Al [18F]F-based radiopharmaceuticals while promoting translation from preclinical to clinical studies. However, commercially available automated radiosynthesizers possess several disadvantages pertaining to the perfor-mance of Al[18F]F radiochelation, including the presence of unsuitable sealed-heating for microvolume re-actions, imprecise liquid handling and lack of a validated kit formulation for automatic production. In order to address these limitations, this study attempted to design, assemble and validate a custom-built radiosynthesizer for the production of clinical-grade Al[18F]F tracers. Due to the special design of the proposed interlinked sealed -heating, the microvolume solution of the reaction mixture was able to be heated above the boiling point without incurring significant volume change. Moreover, high efficiency for [18F]fluoride concentration was achieved with only 150 mu L saline as the eluent with use of the syringe pump, allowing the replication of accurate liquid handling and finally minimizing the volume of the reaction mixture. A validated kit formulation was then developed to bolster the reproducibility and robustness of Al[18F]F chelation. Benefiting from the consumable kit formulation and automated processes optimization, the isolated radiochemical yield for the Al[18F]F tracer was found to be generally higher than those of the reported synthesizer. Furthermore, to demonstrate proof-of -concept, 18F-Alfatide II was then synthesized in large scale (up to 8.31 GBq) with high radiochemical purity (>99 %) and molar activity of 10.6-83.2 GBq/mu mol. 18F-Alfatide II exhibited favorable pharmacokinetics in lung cancer patients for clinical trials, demonstrating high and specific accumulation in tumor tissues.