211At及131I标记尼妥珠单抗的荷瘤小鼠体内治疗研究

Preliminary Treatment Study of 211At and 131I Labeled Nimotuzumab in Tumor-bearing Mice

  • 摘要: 以靶向表皮生长因子受体(EGFR)的尼妥株单抗(nimotuzumab)为载体,开展211At和131I一步法标记流程的建立和对荷U87MG胶质瘤裸鼠的初步治疗研究。结果表明,标记率约95%,在磷酸缓冲液(PBS)和10%胎牛血清(FBS)中能保持一定稳定性;瘤内注射24 h后,药物在肿瘤的放射性摄取率仍然能保持在(28.2±4.7)%ID·g-1131I/211At-ATE-nimotuzumab均可对U87MG实体瘤的生长产生明显的抑制作用,且呈剂量相关性;整个治疗过程中,药物对荷瘤鼠体重无明显影响并且有效地延长了生存时间;相较而言,20 μCi的211At-ATE-nimotuzumab治疗组荷瘤小鼠中位生存时间长于200 μCi 131I-ATE-nimotuzumab治疗组荷瘤小鼠的中位生存期,分别为35 d和31.6 d。该工作进一步确定了α核素211At在放射性靶向治疗研究中的潜力,为相关药物的临床前基础研究提供了重要参考。

     

    Abstract: Using nimotuzumab targeting epidermal growth factor receptor (EGFR) as carrier, we have established a one-step labeling process for 211At and 131I and performed a preliminary treatment study on tumor-bearing mice. The labeling rate both were about 95%, and related radiolabeling complexes could maintain stability in PBS and FBS. The distribution showed that tumor uptake was still maintained to (28.2±4.7) %ID·g-1 after 24 h at intratumoral injection. The therapeutic effect of 131I/211At -ATE-nimotuzumab in U87MG glioma-bearing nude mice was further evaluated. The two labeled drugs can significantly inhibit the growth of solid tumors in a dose-dependent manner with no significant effect on the body weight of mice, effectively prolonging the survival time of subjects. In comparison, the median survival time of tumor-bearing mice in the 211At-ATE-nimotuzumab group at 20 μCi was longer than that in the 131I-ATE-nimotuzumab group at 20 μCi (35 days and 31.6 days). This work further confirmed that the α-nuclide 211At has great potential in the research of radioactive targeted therapy, and can provide an important reference for the preclinical basic research of related drugs.

     

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