99Tcm标记Gd-DTPA-DG及其在裸鼠体内的生物分布

摘要

Objective To observe the stability and biodistribution of 99 Tcm 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. Methods To form 99 Tcm-Gd-DTPA-DG , the labelling conditions such as Gd-DTPA-DG quality, SnCl2 · 2 H2 O 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 99 Tcm-Gd-DTPA-DG. Results When taking 10 mg Gd-DTPA-DG,0. 6 mg SnCl2 · 2H2O,pH＜2,adding 37 MBq Na99 TcmO4 ,then reacting in boiling water for 30 min, the radiochemical purity of 99Tcm-Gd-DTPA-DG can reach to 98. 5％ and remain 96. 2％ placed at room temperature for 6 h. 99TcmGd-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. Conclusion 99 Tcm labeled the paramagnetic MR contrast agent Gd-DTPA-DG is feasible. The labeled agent shows excellent tumor targeting in nude mice in vivo. 99 Tcm-Gd-DTPA-DG is potential for a SPECT(single photon emission computed tomography)-MRI dual-modality imaging probes.%目的 探讨锝(99Tcm)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99Tcm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99Tcm -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 mg Gd-DTPA-DG、0.6 mg SnCl2·2H2O,在pH值小于2时加入新淋洗的Na99TcmO4洗脱液(37 MBq),沸水反应30 min所得99Tcm -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99Tcm -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99Tcm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.