摘要
Abstract
Objective:To establish an automated synthesis process for 18F-DPA-714,validate its quality,and conduct preliminary imaging verification of inflammation in a traumatic brain injury model.Methods:Using a Sumitomo CFN fluorine multifunctional synthesis module from Japan,18F-DPA-714 was synthesized via nucleophilic substitution with pre-DPA-714 as the precursor.After optimizing reaction conditions,the product was purified by semi-preparative High-Performance Liquid Chromatography(HPLC)with a mobile phase of 45%acetonitrile/0.1%trifluoroacetic acid(TFA),concentrated on a C18 solid-phase extraction(SPE)cartridge,and finally sterile-filtered to obtain the injectable solution.Three batches of the product underwent quality control(QC)assessments,including radiochemical yield(RCY),radiochemical purity(RCP),pH,residual solvents(acetonitrile,K2.2.2),sterility,and bacterial endotoxin levels.Results:The results indicated that the optimal synthesis conditions for 18F-DPA-714 were as follows:the reaction temperature is 100℃,the reaction time is 10 min,and the precursor amount is 2 mg.The total synthesis time,from the drying of 18F-fluoride to the final product,was approximately 45 min,exhibiting an uncorrected radiochemical yield of(42.5±3.2)%(n=30)and a radiochemical purity＞99%.The final formulation was a clear,colorless solution(pH 5.57.0)with residual acetonitrile＜0.04%and K2.2.2＜50 μg/mL,ethanol content＜10%,specific activity 80-102 GBq/μmol,and it complied with the Chinese Pharmacopoeia standards for sterility and bacterial endotoxins.Preliminary inflammatory imaging validation in traumatic brain injury models in this study further confirmed the potential of 18F-DPA-714 for neuroinflammation assessment.The preparation process adopted in this work was completed using an existing automated synthesis module(Sumitomo CFN),demonstrating good reproducibility(n≥30)and stable,reliable product quality,which can meet the quality requirements for future clinical applications.关键词
18F-DPA-714/TSPO显像剂/自动化合成/质量控制Key words
18F-DPA-714/TSPO imaging agent/automated synthesis/quality control分类
能源科技
