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

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68 Ga-NOTA-JR11.采用放射性高效液相色谱法对68 Ga-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 68 Ga-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 68 Ga-NOTA-JR11,观察注射后60 min时microPET显像情况.结果 成功制备68 Ga-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 68 Ga-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 68 Ga-NOTA-JR11. 68 Ga-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 68 Ga-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 ( radio-chemical purity:95％) in different buffers within 150 min. The biodistribution was basically consistent with microPET imaging results. 68 Ga-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 68 Ga-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.