回旋加速器固体靶生产^(68)Ga及其标记药物的自动化合成  

^(68)Ga production with cyclotron solid target and automated synthesis of ^(68)Ga labeled drugs

作　　者：赵海涛 吕春 王成[1] 杜富强 胡周密 刘建军[1] Zhao Haitao;Lyu Chun;Wang Cheng;Du Fuqiang;Hu Zhoumi;Liu Jianjun(Department of Nuclear Medicine,Renji Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 200127,China)

机构地区：[1]上海交通大学医学院附属仁济医院核医学科,上海200127

出　　处：《中华核医学与分子影像杂志》2023年第8期492-495,共4页Chinese Journal of Nuclear Medicine and Molecular Imaging

基　　金：上海交通大学"交大之星"计划医工交叉研究基金(YG2022QN019);上海市核酸化学与纳米医学重点实验室"临床+"卓越项目(2021ZYA023)。

摘　　要：目的基于低能医用回旋加速器固体靶系统进行^(68)Ga的生产及其标记药物的自动化合成。方法通过电沉积将68Zn电镀于靶片表面。依据68Zn(p,n)^(68)Ga核反应原理,采用10 MeV医用回旋加速器固体靶系统轰击68Zn(30μA,30 min)以生产^(68)Ga,测定其活度、核纯度、半衰期及纯化后金属杂质含量等。利用^(68)Ga分别进行^(68)Ga-前列腺特异膜抗原(PSMA)-11和^(68)Ga-1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸-D-苯丙氨酸1-酪氨酸3-苏氨酸8-奥曲肽(DOTATATE)的自动化合成,并对药物的性状、浓度、pH值、放化纯、无菌和细菌内毒素等进行质量控制分析。结果68Zn电镀质量为(43.71±0.87)mg(n=35),照射后^(68)Ga产量为(10.96±0.67)GBq(n=35),测定的半衰期为(67.64±0.06)min(n=7),γ能谱仪只检测到511 keV能量峰。经纯化获得^(68)Ga纯品(6.85±0.12)GBq(n=35),未衰减校正纯化效率为(62.46±0.96)%(n=35),Zn和Fe金属杂质含量分别为(0.18±0.06)和(1.25±0.43)μg/GBq(n=5),符合欧洲药典规定。自动化合成^(68)Ga-PSMA-11和^(68)Ga-DOTATATE各3批,其产量、放射性浓度与放化纯分别为(3.54±0.14)和(2.74±0.20)GBq、(294.97±11.58)和(228.17±16.32)GBq/L、(99.73±0.11)%和(99.45±0.25)%,无菌与细菌内毒素检测均合格。结论通过低能医用回旋加速器固体靶系统及自动化纯化与合成模块成功制备了高产量、质量合格的^(68)Ga核素及其标记药物,可为临床提供有力保障。Objective To produce ^(68)Ga and automatically synthesize ^(68)Ga-labeled drugs based on low-energy medical cyclotron solid target system.Methods 68Zn was electroplated on the surface of the target by electrodeposition.According to the principle of 68Zn(p,n)^(68)Ga nuclear reaction,68Zn was irradiated by the 10 MeV medical cyclotron solid target system(30μA,30 min)to produce ^(68)Ga,and the activity,nuclear purity,half-life and content of metal impurities of purified product were determined.^(68)Ga-prostate specific membrane antigen(PSMA)-11 and ^(68)Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-D-Phe1-Tyr3-Thr8-octreotide(DOTATATE)were synthesized automatically using ^(68)Ga respectively,and the quality control analyses of drug properties,concentration,pH,radiochemical purity,sterility and bacterial endotoxin were carried out.Results The electroplating mass of 68Zn was(43.71±0.87)mg(n=35),the yield of ^(68)Ga after irradiation was(10.96±0.67)GBq(n=35),and the measured half-life was(67.64±0.06)min(n=7).Only 511 keV energy peak was detected by the gamma spectrometer.After purification,(6.85±0.12)GBq(n=35)of pure ^(68)Ga was obtained,and the purification efficiency was(62.46±0.96)%(non-attenuated correction,n=35).The metal impurity contents of Zn and Fe were(0.18±0.06)and(1.25±0.43)μg/GBq(n=5),which met the requirements of European Pharmacopoeia.Three batches of ^(68)Ga-PSMA-11 and ^(68)Ga-DOTATATE were automatically synthesized,with the yield,concentration and radiochemical purity of(3.54±0.14)and(2.74±0.20)GBq,(294.97±11.58)and(228.17±16.32)GBq/L,(99.73±0.11)%and(99.45±0.25)%,respectively.Both sterility and bacterial endotoxin were qualified.Conclusion High-yield and qualified nuclide ^(68)Ga and ^(68)Ga-labeled drugs are successfully prepared through the low-energy medical cyclotron solid target system and the automated purification and synthesis module,which provide a strong guarantee for clinical practice.

关 键 词：回旋加速器 固体靶 镓放射性同位素 同位素标记 质量控制 

分 类 号：TQ460.3[化学工程—制药化工]