^131I标记Tyr-GX1在荷瘤裸鼠体内分布和显像研究

目的：设计、合成酪氨酸（Tyr）修饰的肿瘤血管靶向肽GX1,研究^131I标记短肽Tyr-GX1在荷人胃癌裸鼠体内的生物学分布与显像,探讨^131I-Tyr-GX1短肽作为肿瘤血管靶向诊治药物的可能性。方法：利用Iodogen碘标法对Tyr-GX1进行131I标记,检测其标记率和体内外稳定性;建立荷人胃癌裸鼠动物模型,尾静脉注射标记肽,分别进行体内生物学分布实验和肿瘤显像实验,结果用PASW Statistics18.0统计软件进行分析。结果：1）.纸层析法结果计算表明,^131I-Tyr-GX1肽的标记率和放化纯均达90%以上;24 h稳定性测试表明,^131I-Tyr-GX1在室温下存放以及与人血清、鼠血清、PBS等溶液混合,其标记率仍然都维持在90%左右,说明其具有良好的体内外稳定性;2）.荷瘤裸鼠体内生物学分布研究显示：标记肽在荷瘤裸鼠双肾放射性计数测量最高;其次是肝脏、肿瘤等组织;脑、骨、肌肉组织放射性计数含量较低,给药24 h时,肿瘤/肌肉（T/M）、肿瘤/血液（T/Bl）、肿瘤/脑组织（T/Br）的放射性比值分别是5.78、4.06和23.01;3）.体内SPECT显像结果显示：尾静脉注射^131I-Tyr-GX1肽后4 h肿瘤部位已开始显影,并随时间的延长,显像逐渐清楚,至18 h时,肿瘤显像最清晰。结论：应用Iodogen碘标法成功标记Tyr-GX1短肽;尾静脉注射^131I-Tyr-GX1后,肿瘤部位可以出现放射性浓聚,表明^131I-Tyr-GX1短肽可以靶向结合于肿瘤部位,有望成为新一种胃肠道肿瘤诊断与治疗的药物。

Biodistribution and Imaging of ^131I-labelled Tyr-GX1 Peptide Homing to Tumor Vessels in Nude Mice Bearing Tumors

Objective： To design and modify tumor vasculature homing peptide GX1 with tyrosine （Tyr）, and evaluate the possibility of ^131I-Tyr-GX1 peptide as tumor targeted radiotracer by analysing the biodistfibution and ECT imaging of ^131I- labelled GX1 peptide in nude mice bearing human gastric tumors. Methods： Tyr-GX1 peptide was labelled with ^131I by Iodogen method under the optimum labelling conditions, then the labeling efficiency and the stability were detected in vivo and in vitro. Nude mice bearing tumor xenografts of human gastric carcinoma were intravenously injected with ^131I-Tyr-GX1 via a vein of mouse tail, and SPECT imaging and biodistribution were performed. The percent injected dose per gram （%ID/g） of different organs or tissues and T/NT ratio were measured, then the data was analysed with PASW Statistics18.0. Results： 1）.Paper chromatography showed that the labeling efficiency and the radiochemical purity of ^131I- labelled GX1 peptide were over 90 %. The stability of ^131I- labelled GX1 peptide in human serum, mouse serum, PBS buffer solution were maintained 90 % in 24 h; 2）. In biodistribution, high radioactivity was found in kidney, then in the liver, tumor, and lower radioactivity was found in muscle, brain and bone. Tumor/muscle （T/M）, tumor/blood （T/B1）, tumor/brain （T/Br） were 5.78, 4.06 and 23.01 respectively at 24 h. 3）. The SPECT imaging showed increased ^131I- labelled GX1 peptide uptake in the tumor from 4 h to 24 h gradually after injection. Conclusions： Tyr-GX1 peptide could be labelled with^131I by Iodogen method easily and effectively.^ 131I- labelled GX1 peptide showed perfect tumor-targeting efficacy in vivo, which indicted it may be developed as a new promising gastrointestinal turnor targeted radiotracer.