90Y-抗人成骨肉瘤单抗对人成骨肉瘤裸鼠移植模型的治疗观察
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Effect of radioimmunotherapy with Yttrium-90 monoclonal antibody labeled on human osteosarcoma in nude mice osteosarcoma model
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    摘要:

    目的:观察90Y标记的抗人成骨肉瘤单克隆抗体(OSMcAb)对人成骨肉瘤裸鼠移植模型的放射免疫治疗作用。方法:采用EDTA淋洗法从90Y发生器上制备游离90Y,并用DTPA环酐法将90Y标记OSMcAb。标记单抗进行体外靶细胞结合实验以验证标记后单抗蛋白活性保持程度,应用自制的人成骨肉瘤细胞系HOS-8603接种裸鼠建立人成骨肉瘤的裸鼠移植模型,使用90Y-OSMcAb,对此模型进行导向治疗观察。结果:(1)EDTA淋洗法制备90Y纯度高,其相对含量可达99.997%;(2)单克隆抗体的90Y标记率达90%以上,抗体蛋白活性保持82.3%;(3)治疗结果表明治疗组肿瘤明显小于对照组,原肿瘤的指数生长规律遭到破坏,治疗组生存期明显长于对照组;(4)组织学切片显示治疗组肿瘤有广泛坏死,PcNA免疫组化显示治疗组肿瘤细胞增殖受到明显抑制。结论:经单抗特异导向的90Y在体内有很好的杀肿瘤效应,使用核素标记该单抗对骨肉瘤进行放射免疫实验治疗是成功的。

    Abstract:

    Objective: To observe the effects of radioimmunotherapy with 90Y-OSMcAb on human osteosarcoma in nude mice osteosarcoma model. Methods:The monoclonal antibody labeled with carrier-free 90Y by singcyclic DTPA-chelation. The carrier-free 90Y was eluted from 90Y generator. The radioimmuno-complex was proven to combine with osteosarcoma cell. Osteosarcoma cells from human osteosarcoma cell line were implanted into the nude mice which could grow and reproduce in nude mice bodies. The therapy effects with 90Y-OSMcAb and 90Y-Cl3 on human osteosarcoma in nude mice model were observed. Results: (1) The 90Y activity was higher while the contumination of 90Sr was less than 0.0031%; (2) The efficiency of 90Y-labeled antibodies was over 90%,the activity of labeled antibody maintained 82.3%; (3) Tumor size of all 90Y-antibody-treated model was significantly less than that of all 90Y-Cl3-treated model, the average survival time of the mice of the 90Y-antibody-treated group was significantly longer than that of the 90Y-Cl3-treated group; (4) In the tissue sections extensive necrosis was observed in all 90Y-antibody-treated tumor, the living tumor cells were immunohistochemically stainable with PcNA. Staining with PcNA in all 90Y-antibody-treated tumor was negtive, but positive in all 90Y-Cl3-treated tumor. Conclusion: OSMcAb post-labeled targets osteosarcoma structures. 90Y-OSMcAbs can successfully treat osteosarcoma in nude mice.

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