99mTc标记Laminin-YIGSR肿瘤小鼠模型显像的实验研究

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。

Experimental Study on the Imaging of Eldrich Ascites Tumor Bearing Mice with 99mTc Labeled Laminin-YIGSR

Objective To evaluate the applied value of ~(99m)Tc-YIGSR as a new tumor radiotracer in the receptor imaging of Eldrich ascites tumor.Methods By using S-Acetly-NHS-MAG_3 as a chelator,~(99m)Tc was labeled on a peptide fragment YIGSR;The biodistribution experiments on tumor bearing mice and the control group were performed;The animal models of tumor bearing group,normal control group,inflammatory control group and obstruction group were imaged.Results Reverse-phase Sep-Pak C_(18) chromatogram revealed that YIGSR could be conjugated to S-Acetly-NHS-MAG_(3) perfectly,and the conjugation could be radiolabelled successfully under the condition of room temperature and normal pH,the radiolabeling rate was 62 % and that of the radiolabeling of YIGSR without chelator was 4% respectively;Biodistribution results revealed that ~(99m)Tc-YIGSR was rapidly cleared up,mainly from the kidneys,then the liver;After injecting the radiotracer into the tumor bearing mice,there was radioactivity uptake at the tumor tissue at 15 min,which reached the highest uptake at 3rd h with a tumor to contralateral limb ratio of 11.36.As the radiotracer was slowly cleared,the tumor/contralateral ratio was decreased to 7.50 at 8th h.The tumor uptake was significantly lower in the obstruction group with a tumor to contralateral ratio of 4.61 at 3rd h and 0.89 at 8th h respectively.In the inflammatory group,the tumor to contralateral ratio was 3.72 at 3rd h and 1.29 at 8th h respectively.Compared with inflammatory group and control obstruction group,the ratio of tumor/contralateral in tumor group had significant difference(P<0.01).Conclusion Using S-Acetly-NHS-MAG_(3), we can radiolabel the laminin peptide fragment YIGSR with ~(99m)Tc successfully.~(99m)Tc-YIGSR can display tumor tissue rapidly and clearly,and has lots of merits such as high sensitivity and specificity,and high target/non-target ratio.