生长抑素受体拮抗剂68Ga-NOTA-JR11的制备及其microPET显像  

Preparation and microPET imaging of somatostatin receptor antagonist 68Ga-NOTA-JR11

作　　者：谢卿[1] 朱华[1] 刘特立 郭晓轶 于江媛[1] 杨志[1] Xie Qing;Zhu Hua;Liu Teli;Guo Xiaoyi;Yu Jiangyuan;Yang Zhi(Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education),Department of Nuclear Medicine,Peking University Cancer Hospital&Institute,Beijing 100142,China)

机构地区：[1]北京大学肿瘤医院暨北京市肿瘤防治研究所核医学科、恶性肿瘤发病机制及转化研究教育部重点实验室,100142

出　　处：《中华核医学与分子影像杂志》2019年第8期473-477,共5页Chinese Journal of Nuclear Medicine and Molecular Imaging

基　　金：国家自然科学基金( 81571705, 81671733, 81871386)

摘　　要：目的制备生长抑素受体(SSTR)拮抗剂68Ga-1,4,7-三氮杂环壬烷-1,4,7-三乙酸(NOTA)-JR11,并行生物分布和microPET显像研究。方法将1 ml含68GaCl3(148 MBq)的HCl(0.05 mol/L)加入至65μl NaAc缓冲液(1 mol/L)和4μg前体NOTA-JR11中,95℃反应15 min,经Sep-Pak?C18 Light柱纯化后得到68Ga-NOTA-JR11。采用放射性高效液相色谱法对68Ga-NOTA-JR11进行质量控制分析,测定放化纯和体外稳定性等。取BALB/c小鼠9只,分别注射0.37 MBq 68Ga-NOTA-JR11,观察注射后5、30和60 min时药物的生物分布(每个时间点3只),计算每克组织百分注射剂量率(%ID/g);另取BALB/c小鼠1只,注射14.8 MBq 68Ga-NOTA-JR11,观察注射后60 min时microPET显像情况。结果成功制备68Ga-NOTA-JR11,标记用时15 min,产率为90%,纯化后的放化纯大于99%,比活度为6.10 GBq/μmol,在多种缓冲溶液中放置150 min内放化纯仍在95%左右。体内生物分布与microPET显像结果基本一致,药物主要经肾脏代谢,注射后60 min肝脏摄取较低,为(0.75±0.26)%ID/g。结论68Ga-NOTA-JR11具有制备快速、产率高、放化纯高等特点,其生物分布和显像结果可为神经内分泌肿瘤SSTR显像研究提供进一步的基础信息。Objective To prepare a novel somatostatin receptor(SSTR)antagonist 68Ga-1,4,7-triazacyclononane-1,4,7-triacetic acid(NOTA)-JR11(Cpa-c(D-Cys-Aph(Hor)-D-Aph(Cbm)-Lys-Thr-Cys)-D-Tyr-NH2)tracer and observe its biodistribution and microPET imaging in mice.Methods One ml HCl(0.05 mol/L)containing 68GaCl3(148 MBq)was added into 65μl NaAc(1 mol/L)and 4μg NOTA-JR11.The mixture reacted at 95℃for 15 min,and then was purified with Sep-Pak?C18 Light column to obtain 68Ga-NOTA-JR11.68Ga-NOTA-JR11 was subjected to quality control analysis including radiochemical purity and in vitro stability by radio-high performance liquid chromatography.Biodistribution of 68Ga-NOTA-JR11(0.37 MBq)in BALB/c mice(n=9)at 5,30,60 min postinjection were observed(n=3 for each time point),and the percentage activity of injection dose per gram of tissue(%ID/g)was calculated.68Ga-NOTA-JR11(14.8 MBq)microPET imaging of BALB/c mice(n=1)at 60 min postinjection was observed.Results 68Ga-NOTA-JR11 was obtained successfully within 15 min,with yielding rate of 90%,radiochemical purity of more than 99%,and specific activity of 6.10 GBq/μmol.The tracer showed excellent stability(radiochemical purity:95%)in different buffers within 150 min.The biodistribution was basically consistent with microPET imaging results.68Ga-NOTA-JR11 was metabolized through the kidneys and had low uptake in the liver((0.75±0.26)%ID/g)at 60 min postinjection.Conclusions 68Ga-NOTA-JR11 can be prepared rapidly,with high yielding rate and radiochemical purity.Biodistribution and imaging results provide basic information for the further study of somatostatin receptor imaging in neuroendocrine tumors.

关 键 词：拮抗剂 受体 生长抑素 同位素标记 镓放射性同位素 正电子发射断层显像术 小鼠 

分 类 号：R81[医药卫生—放射医学]