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磁共振对比剂Gd-DTPA-DG的制备及动物实验研究

ISSN号：1671-8348
期刊名称：《重庆医学》
时间：0
分类：R817.4[医药卫生—影像医学与核医学;医药卫生—放射医学;医药卫生—临床医学]
作者机构：[1]泸州医学院附属医院核医学科,四川泸州646000
相关基金：2009年国家自然科学基金资助项目（30970858）; 2010年四川省卫生厅资助项目（100277）

作者：黄占文[1], 张伟[1], 陈跃[1], 蔡亮[1], 曹丰[1], 丁志凌[1], 何菱[2]

关键词：锝, 放射性核素显像, 肿瘤, 分子影像, 二乙三胺五乙酸-脱氧葡萄糖钆盐, 双模式影像探针, technetium, radionuclide imaging, tumor, molecular imaging, Gd-DTPA-DG, dual-modality imaging probes

中文摘要：

目的探讨锝（^99Tc^m）标记顺磁性脱氧葡萄糖类MRI对比剂二乙三胺五乙酸-脱氧葡萄糖钆盐（Gd-DTPA-DG）的稳定性及在荷瘤裸鼠体内的生物分布,寻找一种核素与磁共振双模式影像探针。方法对Gd-DTPA-DG进行^99Tc^m标记,并对需要的Gd-DTPA-DG、氯化亚锡（SnCl2·2H2O）用量,pH,温度采用正交实验设计,确定最佳标记条件。采用薄层纸层析法（TLC）分析标记率,体外放置6 h,观察标记物的稳定性。将标记的^99Tc^m-Gd-DTPA-DG注入裸鼠体内,10、30 min及1、2、4、24 h后断头处死裸鼠,测定血液、心脏、脑、肝脏、脾脏、肺脏、肾脏、小肠、肌肉、肿瘤中的每克组织百分注射剂量率（%ID/g）。结果取10 mgGd-DTPA-DG、0.6 mg SnCl2·2H2O,在pH值小于2时加入新淋洗的Na^99Tc^mO4洗脱液（37 MBq）,沸水反应30 min所得^99Tc^m-Gd-DTPA-DG放化纯度最高,可达98.5%,体外放置6 h,放化纯度仍大于96%。尾静脉注射^99Tc^m-Gd-DTPA-DG 2 h后,裸鼠肿瘤组织的摄取率约为（1.48±0.12）%ID/g,肿瘤与肌肉的放射性摄取比（T/NT）达2.91。结论采用放射性核素^99Tc^m标记顺磁性对比剂Gd-DTPA-DG简单易行;荷瘤裸鼠模型显示其具有良好的肿瘤靶向性,有望成为一种极具发展潜力的新型单光子发射计算机断层显像（SPECT）-MRI双模式影像探针。

英文摘要：

Objective To observe the stability and biodistribution of ^99Tc^m radio-labeled a paramagnetic deoxy-glucose-type MR contrast agent diethylenetriamine pentaacetic acid-gadolinium salt deoxy-glucose（Gd-DTPA-DG） in tumor-bearing nude mice in vivo.MethodsTo form ^99Tc^m-Gd-DTPA-DG,the labelling conditions such as Gd-DTPA-DG quality,SnCl2·2H2O dosage,the reaction medium pH value and reaction temperature were optimized by orthogonal experimental design.The radio-labeling efficiency was measured by thin layer chromatography（TLC）.The bio-distribution was observed by the tumor and other major organs were taken out from nude mice at 10,30 min and 1,2,4,24 h respectively after caudal vein injection of ^99Tc^m-Gd-DTPA-DG.ResultsWhen taking 10 mg Gd-DTPA-DG,0.6 mg SnCl2·2H2O,pH2,adding 37 MBq Na^99Tc^mO4,then reacting in boiling water for 30 min,the radiochemical purity of ^99Tc^m-Gd-DTPA-DG can reach to 98.5% and remain 96.2% placed at room temperature for 6 h.^99Tc^m-Gd-DTPA-DG accumulated in the tumor to a higher level than other organ at 2 h,the uptake was about（1.48±0.12）%ID/g,and the radio-uptake ratio of tumor to muscle（T/NT）was reached 2.91.Conclusion99Tcm labeled the paramagnetic MR contrast agent Gd-DTPA-DG is feasible.The labeled agent shows excellent tumor targeting in nude mice in vivo.99Tcm-Gd-DTPA-DG is potential for a SPECT（single photon emission computed tomography）-MRI dual-modality imaging probes.

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