^(188)Re标记VEGF多肽片段的荷瘤裸鼠体内分布及显像研究  

Imaging and biodistribution of rhenium-188 labeled peptide encoded by VEGF_(189) exon 6 in tumor bearing nude mice

作　　者：秦浙学[1] 李前伟[1] 刘广元[1] 谢赣丰[1] 罗朝学[1] 黄定德[1] 

机构地区：[1]第三军医大学西南医院核医学科,重庆400038

出　　处：《第三军医大学学报》2009年第6期487-490,共4页Journal of Third Military Medical University

基　　金：国家自然科学基金(30400114);第三军医大学科研基金(2004)~~

摘　　要：目的探讨188Re标记VEGF189外显子6编码的多肽(QKRKRKKSRYKS)的方法、标记物在荷瘤裸鼠体内的分布及显像。方法以S-acetyl-MAG3为双功能螯合剂,正交设计法寻找188Re标记多肽QKRKRKKSRYKS的最佳条件;研究标记物在荷卵巢癌SKOV3裸鼠的体内分布,并在不同时间行SPECT平面显像。结果采用SPSS13.0进行分析。结果188Re标记QKRKRKKSRYKS在最佳标记条件下的标记率为(73.1±5.5)%,HPLC纯化后放射化学纯度>95%,且受体结合活性良好;标记物室温下放置24h,其放射化学纯度为(91.76±1.36)%;尾静脉注射标记物后,0.5h荷瘤裸鼠肿瘤部位开始出现放射性浓聚,1h浓聚更为明显,肿瘤放射性摄取为(1.846±0.511)%ID/g,肿瘤/对侧肌肉组织比值达(2.43±0.30)。此外,肝脏、小肠、肾脏及膀胱等部位也可见明显的放射性浓聚,但3h后肿瘤部位的放射性浓聚影基本消退。结论188Re-MAG3-QKRKRKKSRYKS能明显聚集于肿瘤组织。Objective To investigate the labeling method of peptide encoded by VEGF189 exon 6 （QKRKRKKSRYKS） with ^188Re and evaluate the biodistribution and imaging of the lSSRe labeled agents in tumor bearing nude mice. Methods We used S-acetyl-MAG3 as the bifunctional chelating agent to label QKRKRKKSRYKS with rhenium-188, and the labeling conditions were optimized according to an orthogonal design. The tumor bearing mice were injected via tail veins with radiolabeled peptide. The percent injected dose per gram （% ID/g） of different organs and the T/NT ratios were measured and calculated. The tumors were imaged with SPECT. All the data were analyzed with SPSS13.0. Results The optimized condition was tested and the corresponding labeling efficiency was 73.1 ± 5.5%. After purification the radiochemical purity of the labeled peptide was over 95% , meanwhile the labeled agents retained a good stability and binding activity with KDR. In vivo, the uptakes of the labeled peptides in kidneys, liver, and intestine were with high radioactivity. SPECT imaging showed that labeled peptide accumulated in the tumor site. The uptake at the tumor sites was （1. 846 ± 0. 511 ） % ID/g at 1 h while the tumor/muscle ratio was 2.43 ± 0.30. Conclusion ^188Re can successfully label MAG3-QKRKRKKSRYKS, The labeled peptides accumulate in tumors, ^188Re-MAG3- QKRKRKKSRYKS may be a promising agent for tumor imaging and therapy.

关 键 词：VEGF 188铼 肿瘤显像 

分 类 号：R811.5[医药卫生—放射医学] R817[医药卫生—临床医学]