^(131)I-c(RGD)_2在荷不同类型肿瘤小鼠中的生物分布与显像研究

The Biodistribution and Imaging of ^(131)I-c(RGD)_2 in Mice Bearing Different Kinds of Tumor

[目的]对131I标记的新型环RGD肽二聚体[c(RGD)2]在荷B16和U87两种小鼠肿瘤模型中的生物分布和显像进行研究,以探讨其应用于肿瘤血管生成显像和治疗的可能性。[方法]采用ChT法对c(RGD)2进行131I标记,标记产物经Sephadex G10分离纯化;建立荷黑色素瘤(B16)和荷人神经胶质瘤(U87)的动物模型,进行体内生物分布和显像研究,分析131Ic(RGD)2在不同肿瘤中的摄取差异。[结果]131I对c(RGD)2的标记率为(76.35±2.33)%,经Sephadex G10分离纯化后放射化学纯度达(95.20±3.25)%;静脉注射24h后,131I-c(RGD)2在B16和U87肿瘤中的摄取率分别为(0.18±0.02)ID%/g和(0.30±0.03)ID%/g,两者具有显著统计学差异(P<0.001);肿瘤与肌肉(T/M)摄取比值分别为4.42±1.70与4.29±1.32,肿瘤与血液(T/B)摄取比值分别为2.27±0.45与5.00±0.63。荷B16肿瘤小鼠全身显像在静脉注射24h后可见肿瘤影像,但肿瘤与周围组织对比度较低;而荷U87肿瘤裸鼠全身显像静脉注射3h后即可见清晰的肿瘤影像,随时间延长,肿瘤与周围组织对比度增高。[结论]131I标记的新型环RGD肽二聚体在肿瘤组织中有较高的摄取率,但在不同肿瘤中的摄取有较大的差异,其在U87肿瘤中摄取率更高,对U87肿瘤显像清晰,有可能应用于肿瘤血管生成显像和治疗效果预测。

[Purpose] To study the biodistribution and imaging of a 131I labeled novel disulfide bridged RGD peptide dimmer [c（RGD）2] in mice bearing B16 and U87 tumors,and to investigate its possibility for tumor angiogenesis imaging and therapy. [Methods] c（RGD）2 was labeled with 131I by ChT method and purified with Sephadex G10. The tumor models of mice bearing meloma BI6 and glioma U87 xenografts were established. The biodistribution and imaging were performed by injecting the labeled peptide into the tumor models. The difference of 131I-c（RGD）2 uptake in two kinds of tumor was analyzed. [Results ] The 13q labeling efficiency and radiochemical purity were （76.35±2.33）% and （95.20±3.25）%,respectively. The tumor uptake of the labeled peptide in BI6 and U87 at 24h post-injection were（0.18±0.02）ID%/g and （0.30±0.03）ID%/g,with significant difference （P〈0.001）, The T/Ms were 4.42±1.70 and 4.29±1.32. The T/Bs were 2.27±0.45 and 5.00±0.63. For meloma B16,tumor was visualized only when 24h post-injection and the contrast was poor,whereas tumor was clear for glioma U87 3h post-injection and the contrast was sharper with time lasted. [Conclusion] The novel 13labeled peptide c（RGD）2 has high uptake in tumor but the difference of uptake in different tumors is significant. 13±I-c（RGD）2 has high uptake in glioma U87 and the images of U87 tumor is clear,which suggests its possibility in tumor angiogenesis imaging and therapy.