摘要
目的:验证AllinOne模块自动化制备多巴胺转运蛋白(dopamine transporters,DAT)显像探针18氟-氮-(3-氟丙基)-2β-甲酯基-3β-(4′-碘苯基)去甲基托烷[^(18)F-N-(3-fluoropropyl)-2β-carbomethoxy-3β-(4′-iodophenyl)nortropane,^(18)F-FP-CIT]的稳定性和效率,同时验证产物的安全性和靶向性及对大鼠基底节区的显像作用。方法:以氮-(3′-甲基黄酰氧基丙基)-2β-甲酯基-3β-(4′-碘苯基)去甲托烷作为反应前体,在四丁基氢氧化铵(Tetrabutylammonium Hydroxide,TBAOH)和氨基聚醚(Aminopolyether,Kryptofix 222)催化下,与干燥后的^(18)氟离子(^(18)F^(-))发生氟化反应,产物经高效液相色谱法(high performance liquid chromatography,HPLC)分离纯化,并以最高产率条件建立AllinOne模块的^(18)F-FP-CIT自动化合成程序,并对产物行质量控制检测和大鼠脑微型正电子发射计算机断层扫描系统(micro positron emission computed tomography,Micro PET/CT)显像验证。结果:由AllinOne模块自动化制备的20批次^(18)F-FPCIT的平均合成时间为(72.9±8.9)min,经衰减校正后,合成平均效率为34.8%±5.7%,平均放射化学纯度为98.4%±2.0%。产物^(18)F-FP-CIT的无菌检测、内毒素检测、毒性检测结果以及溶剂残留乙腈含量均符合临床使用标准。Micro PET/CT显像可见正常大鼠基底节均匀、明显的靶向摄取,基底节摄取^(18)F-FP-CIT的程度分别是大脑皮层的2.6倍,小脑的3.7倍,颅骨的4.1倍。结论:AllinOne模块可稳定、迅速、高质地自动化制备DAT显像剂^(18)F-FP-CIT,有望为帕金森病(Parkinson′s disease,PD)等神经退行性变的临床诊疗提供影像技术支持。
Objective:To verify the efficiency and stability of the automated labeling and synthesis of dopamine transporters(DAT)imaging probe,^(18)F-N-(3-fluoropropyl)-2β-carbomethoxy-3β-(4′-iodophenyl)nortropane(^(18)F-FP-CIT),based on the AllinOne module.Meanwhile,to evaluate the safety and targeted ability of the probe and the imaging effect on the basal ganglia of rats.Methods:A fluorination reaction between nitrogen-[3-(methoxy)propyl]-2β-carbonmethoxy-3β-(4′-iodophenyl)nortropane,the reaction precursor,and the dried fluorine-18 ion(^(18)F)was performed,under the catalysis of TBAOH and Kryptofix 222.The product of the reaction was separated and purified by high performance liquid chromatography(HPLC).All the procedure was established on the AllinOne module under the highest yield conditions to perform automated labeling and synthesis of^(18)F-FP-CIT.Quality control tests and Micro PET/CT imaging of rat brain with the automatically synthesized product were carried out.Results:The average synthesis time,efficiency after attenuation correction,and radiochemical purity of 20 batches of^(18)F-FP-CIT made by the AllinOne module was(72.9±8.9)min,34.8%±5.7%,and98.4%±2.0%,retrospectively.The results of sterility test,endotoxin test,toxicity test and residual solvent test of acetonitrile were all met the clinical practice standards.Micro PET/CT imaging showed uniform and obvious targeted uptake of^(18)F-FP-CIT in basal ganglia of normal rats,and the uptake of^(18)F-FP-CIT in basal ganglia was 2.6 times that in cerebral cortex,3.7 times that in cerebellum,and 4.1 times that in skull,respectively.Conclusions:The AllinOne module can automatically label and synthesize DAT imaging probe^(18)F-FP-CIT stably,rapidly,with high-quality,which is expected to provide imaging technical support for the clinical diagnosis and treatment of neurodegenerative changes such as Parkinson′s disease(PD).
作者
屈骞
海汪溪
胡生焰
张敏
陈肖玥
周熠磊
王瑾
胡晓平
李彪
胡佳佳
QU Qian;HAI Wangxi;HU Shengyan;ZHANG Min;CHEN Xiaoyue;ZHOU Yilei;WANG Jin;HU Xiaoping;LI Biao;HU Jiajia(Department of Nuclear Medicine,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China;Beijing Paite Biotechnology Co.,LTD,Beijing 100093,China)
出处
《诊断学理论与实践》
2022年第4期482-489,共8页
Journal of Diagnostics Concepts & Practice
基金
上海市科学技术委员会(浦江人才D类)(21PJD042)
上海市“医苑新星”青年医学人才
上海市临床重点专科建设项目(shslczdzk03403)
国家自然科学基金面上项目(82171976)
