自动化合成N-琥珀酰亚胺-4-[18F]氟苯甲酸酯

Automated synthesis of N-succinimidy-4-[18F] fluoro-benzoic acid ester

目的合成18F同位素标记蛋白质、配体、多肽类的中间体N-琥珀酰亚胺-4-[18F]氟苯甲酸酯(18F-FB)。方法以乙基-4-三甲胺苯甲酸酯-三氟磺酸盐为反应前体,利用正电子发射断层成像(PET)显像药物2-氟-18-氟-2-脱氧-D-葡萄糖(18F-FDG)合成专用模块TRACERlabFX-FDG和多用合成模块TRACERlabFX-FN及其固相萃取系统,基于控制软件的改造,通过亲核取代、氢氧化钠水解、酯化反应"三步法"合成。结果合成18F-FB的总放射性合成时间小于80min,校正后放射化学产率(38±3)%(n=10),放射化学纯度>99%,与标准品19F-FB行HPLC比对分析,在柱平均保留时间Tr=8.515min,两者保留时间基本吻合。结论此法可以成功合成18F-FB,合成工艺成熟稳定,完全实现了自动化合成,为成功实现18F同位素标记蛋白、多肽类大分子物质进而实现PET成像提供了良好条件。

Objective To synthesize the agent of 18-fluorine labeling protein,ligands and polypeptide N-succinimidyl-4-[18F]fluoro-benzoic acidester.Methods The synthesis was performed with the precursors ethyl-4-three trimethylamine benzoate-trifluoromethyl sulfonate for the reaction,using the specific synthesis module TRACERlab FX-FDG for production of PET agent-^18F-FDG and the flexible synthesis module TRACERlab FX-FN with solid phase extraction system,based on the transformation of control software,through the three-step method of nucleophilic substitution,hydroxide hydrolysis with sodium and esterification synthesis.Results The total reaction time was less than 80 minutes,with the corrected radiochemical yield（38±3）%（n=10）,and the radiochemical purity was more than 99%.With the standard 19F-FB HPLC comparative analysis,the average column retention time（Tr =8.515 minutes）,was basically consistent with that of the standard.Conclusion The synthesis is reasonable,stable and fully automated,which may provide a good condition for PET imaging of 18F isotope-labeles protein and peptide macromolecular materias.