131^Ⅰ标记RGD环肽在荷瘤小鼠体内分布与显像研究  

Studies on distribution and imaging of ^(131)Ⅰ-labelled RGD peptide in mice bearing tumors

作　　者：刘红洁[1] 王荣福[1] 张春丽[1] 闫平[1] 付占立[1] 张旭初[1] 郭凤琴[1] 刘萌[1] 于明明[1] 邸丽娟[1] 崔永刚[1] 丁义[2] 

机构地区：[1]北京大学第一医院核医学科,北京100034 [2]北京大学泌尿外科研究所,北京100034

出　　处：《中国医学影像技术》2008年第1期131-133,共3页Chinese Journal of Medical Imaging Technology

基　　金：“973”项目(2006CB705705-1);“985”二期项目(985-2-056);北京大学第一医院科研基金项目

摘　　要：目的研究^(131)I标记含精氨酸-甘氨酸-天冬氨酸的小分子环形肽(cRGD肽)在荷瘤小鼠体内的分布与显像,探讨^(131)I-cRGD肽作为肿瘤诊治药物的可能性。方法利用氯胺T法对cRGD肽行^(131)I标记,建立荷黑色素瘤B16动物模型,分别进行体内分布实验、非标记cRGD肽竞争抑制实验及肿瘤显像研究。结果用统计软件SPSS 12.0进行分析。结果^(131)I-cRGD肽的标记率达90%,放射化学纯度达99%;荷瘤小鼠体内分布实验显示:给药后在血液、肾脏、膀胱有较高的放射性分布,小肠、肝脏、肌肉呈低水平放射性分布,24 h肿瘤/肌肉(T/M)放射性比值=6.34,肿瘤/血液(T/B)放射性比值=1.1。显像结果示:静脉注射^(131)I-cRGD肽后1 h肿瘤开始显影,随时间的延长,影像逐渐清晰,24 h时肿瘤显像最清晰。用非标记cRGD肽进行阻断实验,肿瘤的放射性摄取为(0.969±0.151)%/g,与非阻断组(1.40±0.136)%/g比较具有显著性差异。结论应用氯胺T法可以成功完成^(131)I-cRGD肽标记;尾静脉注射^(131) I-cRGD肽后,肿瘤表现为放射性浓聚,肿瘤对^(131)I-cRGD肽的摄取可被非标记的cRGD肽抑制,表明^(131)I-cRGD肽可与肿瘤新生血管αvβ3受体特异性结合,有望成为一种新型的肿瘤诊治药物。ObJective Due to the selective expression of the αvβ3 integrin in tumors, radiolabelled arginine-glycine-aspartic （RGD） peptides are attractive candidates for tumor targeting. Minor modification of these peptides could have a major impact on in vivo characteristic. By studying the distribution and imaging of 131^Ⅰ labelled cyclic RGD （cRGD） peptide in mice bearing melanoma, we will discuss the possibility of 131^Ⅰ-cRGD peptide as tumor receptor radiotracer. Methods cRGD peptide was labelled with 131^Ⅰ by ChT method under the optimum labelling conditions. 131^Ⅰ-cRGD peptide was injected into the mice via a vein of mouse tail. The percent injected dose per gram （ID%/g） of different organs and T/NT ratios were measured and calculated. The data was analysed with statistical software of SPSS 12. 0. The mice were imaged by SPECT. Resuits The labelling efficiency and the radiochemical purity of 131^Ⅰ-cRGD peptide reached 90% and 99%, respectively. In distribution, higher radioactivity was found in blood, kidney and bladder, and lower radioactivity in small intestine, liver and musule; 24 hour postinjection, T/M= 6.34, and T/B= 1.1. The image of tumor was identified at 1 hour post injection of 131^Ⅰ-cRGD. Images demonstrated increased 131^Ⅰ-cRGD peptide uptake in the tumor after injection 1 to 24 hours gradually. The 131^Ⅰ-cRGD peptide uptake in the tumor showed obviously lower when pretreated with cRGD peptide （P〈0. 05）. Conclusion cRGD peptide could be labelled with 131^Ⅰ effectively. 131^Ⅰ-cRGD peptide accumulated in the tumor after injection via tail vein and its uptake in the tumor showed obviously lower when pretreated with cRGD peptide. The high specificity of 131^Ⅰ- cRGD peptide suggested it may be a new promising tumor receptor radiotracer.

关 键 词：RGD肽 αvβ3受体 131^Ⅰ标记 肿瘤显像 

分 类 号：R-33[医药卫生]