^(18)F-6-L-多巴自动化合成及其初步PET/CT显像

Full Automated Synthesis of ^(18)F-FDOPA and Preliminary PET/CT Imaging

^(18)F-6-L-多巴(^(18)F-FDOPA)作为多巴胺神经递质显像剂,已广泛应用于帕金森病、脑肿瘤以及神经内分泌疾病正电子发射断层(PET)显像诊断和疗效评估。本文使用进口多功能合成仪及其配套卡套和试剂盒,经氟化、还原、碘化、烷基化和水解多步反应,以及HPLC分离纯化,再经无菌过滤器传入产品瓶,得到^(18)F-FDOPA注射液,实现^(18)F-FDOPA自动化生产。并对获得的^(18)F-FDOPA注射液进行质量检测与分析:^(18)F-FDOPA注射液无色、澄清,pH为4~5.5,放化纯度>98%,放射性核纯度>99%,比活度>1.9 GBq/μmol,K2.2.2含量<50 mg/L,甲醇含量<0.01%,乙醇含量<0.01%,二氯甲烷含量<0.01mg/L,二甲基甲酰胺含量<15 mg/L,细菌菌内毒素<0.100 EU/mL,无菌检查结果为0cfu/mL,异常毒性实验为阴性。正常Wistar大鼠腹腔注射卡比多巴30 min后,尾静脉注射^(18)FFDOPA,100min后行microPET/CT扫描,图像显示双侧纹状体可见对称性放射性摄取。进口多功能合成仪可高效、稳定地自动化合成^(18)F-FDOPA,合成时间约80min,校正放化产率为(63.1±3.8)%(n=10),放化纯度大于98%,产品质量达到动物和人体PET显像要求。

^（18）F-fluoro-L-dihydroxyphenylalanine（^（18）F-FDOPA）as a dopamine neurotransmitter imaging agent has been widely used for diagnosis and therapy evaluation of Parkinson＇s disease,brain tumors and neuroendocrine diseases with positron emission tomography（PET）imaging in clinical setting and research.To meet the increasing clinical demand in oncology and neurology,a routine protocol for the automated synthesis of^（18）F-FDOPA with a disposable cassette system on an imported multifunctional synthesizer was studied and discussed.^（18）F-FDOPA was automatically synthesized via a multiple-step reaction,including fluorination,reduction,iodization alkylation and hydrolysis,following purification by using a semi-preparative high-performance liquid chromatography（HPLC）system which was built in the multifunctional synthesizer.After HPLC purification,the purified ^（18）F-FDOPA solution was collected and passed through a sterilizing filter into a collection bottle.The final ^（18）F-FDOPA injection was obtained for quality control（QC）determination.The QC indexes of the final products were detected：the injection was colorless and transparent,pH value was at 4 to 5.5,radiochemical purity〉98%,radionuclide purity 〉99%,specific activity〉 1.9 GBq/μmol,K2.2.2 content〈50 mg/L,methanol content 〈0.01%,alcohol content 〈0.01%,dichloromethane content〈0.01 mg/L,dimethylformamide content〈15 mg/L,bacterial endotoxin test〈0.100 EU/mL,sterility test 0 cfu/mL,and abnormal toxicity test was negative.PET/CT imaging of rats was performed by intravenous injection of ^（18）F-FDOPA half an hour after the intraperitoneal injection of carbidopa,PET/CT scan was performed after100 min post-injection.The imaging of ^（18）F-FDOPA showed symmetry high uptake in the bilateral striatum of normal rats.The decay-corrected radiochemical yield of ^（18）F-FDOPA from the ^（18）F-fluoride was（63.1±3.8）%（n=10）at the end of synthesis（EOS）,the radiochemical purity was no less than 98%,and the total radiosynthesis time was within80 min.The quality control results demonstrated that the quality indexes of the final injection solution met the relevant requirements of radiopharmaceutlcals,which were well-suited for clinical application.An efficient and high reproducible automatic method for the radiosynthesis of ^（18）F-FDOPA with high radiochemical yields and good radiochemical purity is obtained and performed via a multi-step reaction on the multifunctional synthesizer.^（18）F-FDOPA can be used for animal and human PET imaging.