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目的探讨99mTc-YIGSR作为一种新型的肿瘤显像剂在埃氏腹水肿瘤受体显像中的应用价值。方法①制备99mTc-MAG3-YIGSR探针,以S-乙基-琥珀酰亚胺-巯乙苷肽(S-Acetly-NHS-MAG3)为螯合剂,将99mTc标记到层黏素多肽片断YIGSR上;②对肿瘤模型组及封闭模型组行99mTc-YIGSR生物学分布实验;③观察肿瘤模型组、炎症模型组及封闭模型组动物模型显像。结果①反相Sep-Pak C18柱层析结果表明,YIGSR可以很好地与S-Acetly-NHS-MAG3偶联,偶联物在室温及中性条件下可完成99mTc标记,标记率为62%,纯化后放射化学纯度>95%。室温放置1、2、4 h,放射化学纯度分别是91%,86%及81%。未与S-Acetly-NHS-MAG3偶联之YIGSR进行标记时,标记率为4%;②生物学分布结果显示,99mTc-YIGSR在小鼠血液内清除迅速,主要经肾脏排泄,其次为肝脏;③99mTc-YIGSR静脉注入肿瘤模型组小鼠体内后,15 min肿瘤部位有摄取,3 h摄取达高峰,肿瘤/对侧肢体比值为11.36,此后显像剂清除较为缓慢,8 h时下降至7.50。封闭模型组肿瘤细胞的摄取明显低下,肿瘤/对侧肢体比值是4.61(3 h)、0.89(8 h);炎症模型组中,炎症/对侧肢体比值是3.72(3 h)、1.29(8 h)。与炎症模型组及封闭模型组比较,肿瘤模型组3 h、8 h肿瘤/对侧肢体的比值明显增高(P<0.01)。结论通过螯合剂S-Acetly-NHS-MAG3可顺利完成层黏素多肽片段YIGSR的99mTc标记。99mTc-YIGSR用于肿瘤显像具有显像时间早,显像清晰,灵敏度高,特异性强,靶/非靶比值高等特点,是一种有发展前景的新型肿瘤受体显像剂。
Objective To investigate the value of 99mTc-YIGSR as a new tumor imaging agent in the imaging of Ehrlich ascites tumor. Methods ① 99mTc-MAG3-YIGSR probe was prepared and labeled with 99mTc to the laminin YIGSR with S-Acetly-NHS-MAG3 as chelator ; (2) 99mTc-YIGSR biological distribution experiment in tumor model group and closed model group; (3) observation of tumor model group, inflammatory model group and closed model animal model imaging. Results ① The reversed-phase Sep-Pak C18 column showed that YIGSR could be coupled well with S-Acetly-NHS-MAG3. The conjugates could be labeled with 99mTc at room temperature under neutral conditions with the labeling efficiency of 62% , Purified radiochemical purity> 95%. At room temperature for 1, 2 and 4 h, the radiochemical purity was 91%, 86% and 81%, respectively. The labeling rate was 4% when YIGSR was not conjugated with S-Acetly-NHS-MAG3. (2) The biological distribution showed that 99mTc-YIGSR was rapidly cleared in the blood of the mice, mainly excreted by the kidneys, followed by the liver; (3) 99mTc-YIGSR was instilled into the tumor model group at 15 min after instillation of tumor in mice. The uptake peaked at 3 h and the tumor / contralateral ratio was 11.36. After that, the imaging agent was cleared slowly and dropped to 7.50 after 8 h. In the model group, the ratio of tumor to contralateral limb was 4.61 (3 h) and 0.89 (8 h), respectively. The inflammation / contralateral limb ratio was 3.72 (3 h), 1.29 (8 h) h). Compared with the model group and the model group, the ratio of tumor to contralateral limb in 3 h and 8 h of tumor model group was significantly higher (P <0.01). Conclusion The 99mTc labeling of the laminin YIGSR was successfully completed by the chelator S-Acetly-NHS-MAG3. 99mTc-YIGSR is a promising tumor receptor imaging agent for tumor imaging with early imaging, clear imaging, high sensitivity, strong specificity and high target / non-target ratio.