消化道肿瘤裸鼠碘-131 标记短肽 Tyr-GX1 的显影特征

Imaging characteristics of Tyr-GX1 labeled with iodine-131 in gastrointestinal tumor nude mice

摘要:

目的 分析碘-131（131I）标记短肽酪氨酸修饰的血管靶向肽（Tyr-GX1）在荷结肠癌与胃 癌裸鼠体内的显影特征。方法 采用Iodogen 碘标法标记Tyr-GX1，检测其标记率和稳定性。建立荷结肠 癌、胃癌裸鼠模型（分别设置为结肠癌组和胃癌组），均注射131I 标记短肽Tyr-GX1，观察24 h 后显影特 征。结果 纸层析法结果表明，131I 标记短肽Tyr-GX1 的标记率较高，为（95.67±0.79）% ；放射化学纯度为 （96.68±1.68）%。24 h 稳定性测试显示，131I 标记短肽分别与人血清、乙二胺四乙酸、生理盐水、半胱氨酸混 合后标记率仍然维持在90% 以上。结肠癌组、胃癌组裸鼠尾静脉注射131I 标记的短肽Tyr-GX1 后8 h 开始裸 鼠右后肢背侧荷瘤部位放射性浓聚较心血池本底升高，并随着时间延长而升高；结肠癌组16 h 时达峰值随后 稍有降低，荷瘤部位和心血池本底放射性摄取比值（T/NT）均>1。结肠癌组与胃癌组T/NT 比值在不同时 间、不同组间及变化趋势上有差异（P <0.05）。随着时间延长，结肠癌组和荷胃癌组裸鼠心、肺、肝、肾、胃、 肌肉、肿瘤、血液和甲状腺组织中Tyr-GX1 摄取率逐渐降低（P <0.05），其中肝、肾组织均具有较高的放射 性。结肠癌组和胃癌组1、6、12 和24 h 肿瘤组织的摄取率均高于心脏、甲状腺、胃和肌肉组织（P <0.05）。 结论 131I 标记短肽Tyr-GX1 对结肠癌和胃癌裸鼠肿瘤血管靶向性较好，与恶性肿瘤组织有较高的结合率， 而结肠癌与胃癌的放射性浓聚和达峰时间有所不同；131I 标记短肽Tyr-GX1 可能在消化道恶性肿瘤血管靶向 诊断和治疗方面具有潜在价值。

Abstract:

Objective To analyze the imaging characteristics of Tyr-GX1 in nude mice bearing colon tumors and gastric tumors. Methods Tyr-GX1 was labeled by Iodogen method, and its labeling rate and stability were detected. The nude mice models of colon cancer and gastric cancer were established by injection of short peptide Tyr-GX1 labeled with iodine 131. The imaging characteristics of Tyr-GX1 were observed 24 hours after labeling. Results The results of paper chromatography showed that the labeling rate of the short peptide Tyr- GX1 labeled with iodine 131 was higher at (95.67±0.79) %, while the radiochemical purity was (96.68±1.68) %.The 24 h stability test showed that the labeling rates of iodine-131-labeled short peptide mixed with human serum, ethylenediaminetetraacetic acid, normal saline or cysteine all remained above 90%. In the colon cancer group and gastric cancer group, 8 hours after the injection of the short peptide Tyr-GX1 labeled with iodine 131 in the tail vein of nude mice, the radioactive concentration in the tumor-bearing part of the right hind limb of the nude mice was higher than that of the cardiac blood pool background and increased with the labeling time. The radioactivity in colon cancer group peaked at 16 h and then decreased slightly, and the ratio of radioactivity at the lesion to that of the cardiac blood pool background (T/NT) was higher than 1. In the gastric cancer group, T/NT at 8 h, 12 h, 16 h and 24 h was lower than that of colon cancer group (P < 0.05). Over time, the uptake rate of Tyr-GX1 in heart, lung, liver, kidney, stomach, muscle, tumor, blood and thyroid tissues of nude mice bearing colon tumors and gastric tumors was gradually reduced (P < 0.05), among which liver and kidney tissues showed high radioactivity. In nude mice bearing colon tumors, the uptake rates of tumor tissue at 1 h, 6 h, 12 h, and 24 h were higher than those of heart, thyroid, stomach and muscle tissue (P < 0.05). In nude mice with gastric tumors, the uptake rates of tumor tissue at 1 h, 6 h, 12 h, and 24 h were higher than those of heart, intestine, thyroid and muscle tissue (P < 0.05). Conclusions the short peptide Tyr-GX1 labeled with iodine-131, has a good targeting effect on tumor blood vessels in nude mice bearing colon tumors and gastric tumors, and has a high binding rate with malignant tumor tissues, while the concentration and peak time of radiation in colon tumors and gastric tumors are different. Thus, Tyr-GX1 labeled with iodine-131 may have a potential value in the diagnosis and treatment of gastrointestinal cancer by targeting tumor blood vessels.