5Suzhou Heyao Biological Technology CO., Ltd, Suzhou, Jiangsu, China4Key Laboratory for Experimental Teratology of the Ministry of Education and Research Center for Experimental Nuclear Medicine, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, ChinaPeople's Hospital, Chenzhou, Hunan, China2Department of PET-CT Center, Chenzhou NO1Department of PET/CT Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China3Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Province Key Laboratory of Molecular Imaging, Wuhan, Hubei, China6Jiangsu Xinrui Pharmaceutical CO., Ltd, Rugao, Jiangsu, China
A custom-built, compact radiosynthesis platform as well as the validated kit formulation has been developed for both flexible Al[18F]F radiochelation optimization and scale up routine production for clinical translation. [Display omitted] • A custom-built platform was architected and validated for Al[18F]F radiochelation. • The kit formulation was developed and validated for on-demand Al[18F]F chelation. • 18F-Alfatide II was automatically synthesized for pre-clinical and clinical studies. The c...更多
A custom-built, compact radiosynthesis platform as well as the validated kit formulation has been developed for both flexible Al[18F]F radiochelation optimization and scale up routine production for clinical translation. [Display omitted] • A custom-built platform was architected and validated for Al[18F]F radiochelation. • The kit formulation was developed and validated for on-demand Al[18F]F chelation. • 18F-Alfatide II was automatically synthesized for pre-clinical and clinical studies. 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 performance of Al[18F]F radiochelation, including the presence of unsuitable sealed-heating for microvolume reactions, 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 µL 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 with high radiochemical purity and molar activity of 10.6–83.2 GBq/μmol. 18F-Alfatide II exhibited favorable pharmacokinetics in lung cancer patients for clinical trials, demonstrating high and specific accumulation in tumor tissues.收起
