去甲肾上腺素转运蛋白显像剂18F-mFBG的自动化合成及其用于嗜铬细胞瘤PET/CT显像的效果评估  

Automatic radiolabeling of the norepinephrine transporter targeted tracer^(18)F-mFBG and evaluation of^(18)F-mFBG PET/CT imaging in pheochromocytoma

作　　者：叶伟健 麻杰 董陈晨 胡俊琪 黎国聪 魏俊杰 钟科 徐浩[1] 王璐[1] Ye Weijian;Ma Jie;Dong Chenchen;Hu Junqi;Li Guocong;Wei Junjie;Zhong Ke;Xu Hao;Wang Lu(Department of Nuclear Medicine,the First Affiliated Hospital of Jinan University,Guangzhou 510630,China;Department of Pharmacy,Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University,Guangzhou 510120,China)

机构地区：[1]暨南大学附属第一医院核医学科,广州510630 [2]中山大学孙逸仙纪念医院药学部,广州510120

出　　处：《中华核医学与分子影像杂志》2023年第9期543-548,共6页Chinese Journal of Nuclear Medicine and Molecular Imaging

基　　金：国家自然科学基金(82102107)。

摘　　要：目的进行去甲肾上腺素转运蛋白(NET)显像剂18F-间氟苄胍(mFBG)的自动化合成,并研究其对嗜铬细胞瘤的显像效果。方法根据mFBG化学结构,设计并合成作为标记前体的叔丁氧羰基保护的金刚烷螺环间碘叶立德苄胍1(1种高价碘叶立德),在AllinOne自动化模块上完成18F标记、脱保护、中和三步反应,经高效液相色谱(HPLC)分离纯化,制剂化后得18F-mFBG产品,再进行质量控制检测。对1例嗜铬细胞瘤术后患者(男,30岁)行18F-mFBG PET/CT显像。结果18F-mFBG合成时间约为70 min,连续5次合成非校正标记产率为(17.8±2.4)%,产品放化纯大于97%,比活度大于59.2 GMBq/μmol,溶剂残留、无菌检测、细菌内毒素检测、异常毒性检测结果均符合《中华人民共和国药典(2020年版四部)》要求。PET/CT显像结果示,嗜铬细胞瘤呈高显像剂摄取表现,病灶定位明确。结论实现了NET显像剂18F-mFBG的自动化标记。自主生成的18F-mFBG质量符合临床要求,在嗜铬细胞瘤的诊断方面具有潜在的临床价值。Objective To fulfill the automatic radiolabeling of the norepinephrine transporter(NET)trancer^(18)F-meta-fluorobenzylguanidine(mFBG),and explore the^(18)F-mFBG PET/CT imaging effect of pheochromocytoma.Methods On the basis of the chemical structure of mFBG,a spirocyclic iodonium ylide was used as the precursor to undergo a 3-step reaction sequence(radiofluorination,deprotection and neutralization)on AllinOne synthesis module.Purification by high performance liquid chromatography and formulation were conducted to generate^(18)F-mFBG.The corresponding quality control tests of^(18)F-mFBG product was performed.Afterwards,a postoperative patient with pheochromocytoma underwent^(18)F-mFBG PET/CT imaging.Results The radiosynthesis was accomplished within 70 min,and^(18)F-mFBG was obtained in(17.8±2.4)%non-decay-corrected radiochemical yield(n=5),with radiochemical purity>97%and molar activity>59.2 GBq/μmol.Sterility test,bacterial endotoxins test,abnormal toxicity test and the acetonitrile residue all met the requirements of Pharmacopoeia of the People′s Republic of China(2020 VolumeⅣ).The^(18)F-mFBG PET/CT imaging disclosed high uptake in pheochromocytoma and clear localization of lesions.Conclusions The automatic radiolabeling of the NET targeted tracer^(18)F-mFBG is successfully realized by commercially available synthesis module,and the production quality meets all requirements for clinical translation.^(18)F-mFBG has a potential to image neuroendocrine lesions in clinical setting.

关 键 词：氟苯类 去甲肾上腺素质膜转运蛋白质类 同位素标记 氟放射性同位素 嗜铬细胞瘤 正电子发射断层显像术 体层摄影术 X线计算机 

分 类 号：R736.6[医药卫生—肿瘤]