双功能制剂^99Tc^m-Gd-DTPA-DG的制备及在荷瘤裸鼠体内的生物分布  

Synthesis and biodistribution of a bi-functional agent ^99Tc^m-Gd-DTPA-DG in tumor bearing nude mice

作　　者：张伟[1] 蔡亮[1] 陈跃[1] 黄占文[1] 丁志凌[1] 曹丰[1] 张莉[1] 何菱[2] 

机构地区：[1]泸州医学院附属医院核医学科,646000 [2]四川大学华西药学院

出　　处：《中华核医学杂志》2011年第2期117-120,共4页Chinese Journal of Nuclear Medicine

基　　金：国家自然科学基金（30970858）;2009年四川高等学校科技创新重大培育项目（09ZZ011）;2008年四川省医学重点学科和重点专科建设项目（2008-17）;四川省杰出青年学科带头人基金（08ZQ026-76） 志谢 四川大学华西医院核医学科李云春教授和宁夏医科大学附属医院核医学科杨吉琴老师

摘　　要：目的 通过99Tcm一步法对DTPA-DG钆盐（Gd-DTPA-DG）进行标记,并观察标记物的稳定性及在荷瘤裸鼠体内的生物分布.方法 首先合成DTPA-DG,再与Gd2O3螯合,制得Gd-DTPADG.采用1.5T超导型MR扫描仪观察Gd-DTPA-DG在荷瘤裸鼠体内的肿瘤靶向效果,用正交实验设计对Gd-DTPA-DG进行99Tcm标记,采用薄层色谱法分析标记率;用SPECT仪观察标记药物在裸鼠体内的分布.裸鼠体内注入标记药物后10,30 min和1,2,4,24 h测定血液、心、脑、肝、脾、肺、肾、小肠、肌肉、肿瘤中的%ID/g.结果 Gd-DTPA-DG在荷瘤裸鼠体内显示出良好的肿瘤靶向效果.99TcmGd-DTPA-DG的放化纯约98.5%;体外放置6 h,放化纯为96.2%.2 h时肿瘤组织显像清晰,肿瘤组织对99Tcm-Gd-DTPA-DG的摄取为（1.48±0.12）%ID/g,肿瘤与肌肉的放射性比值达2.91.结论 MRI示合成的Gd-DTPA-DG可使肿瘤强化;用99Tcm标记Gd-DTPA-DG是可行的,标记物在裸鼠体内显示出良好的肿瘤靶向性,是一种极具发展潜力的SPECT-MRI双功能制剂.Objective To evaluate the stability and biodistribution of a novel SPECT-MRI bi-functional agem 99Tcm-Gd-DTPA-DG in tumor-bearing nude mice. Methods DTPA-DG was synthesized and then conjugated with Gd2O3 to generate Gd-DTPA-DG. The tumor-bearing nude mice were scanned by MRI to evaluate the tumor targeting ability of Gd-DTPA-DG. The orthogonal experiment was applied to optimize pH value of reaction medium and reaction temperature. The radiolabeling efficiency was measured by thin layer chromatography. The distribution of 99Tcm-Gd-DTPA-DG in nude mice was evaluated by scintigrapy in vivo. The % ID/g was measured at different time after intravenous injection of 99Tcm-Gd-DTPA-DG. Results The tumor was significantly enhanced by Gd-DTPA-DG with MRI. The radiochemical purity of 99Tcm-Gd-DTPADG was about 98.5% and remained 96.2% at room temperature for 6 h. The tumor was well visualized by 99TcmGd-DTPA-DG SPECT at 2 h after injection. The tumor uptake was （1.48 ±0.12） %ID/g, and the rumor to muscle radioactivity ratio was 2.91. Conclusions MRI contrast of Gd-DTPA-DG may enhance tumor detection. 99Tcm-labeled Gd-DTPA-DG may be useful for tumor imaging and might have a potential role as a SPECT-MRI bi-functional agent.

关 键 词：脱氧葡萄糖 钆 DTPA 锝 肿瘤移植 小鼠 裸 放射性核素显像 

分 类 号：R73-3[医药卫生—肿瘤]