211At及131I标记尼妥珠单抗的荷瘤小鼠体内治疗研究

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^-1；¹³¹I/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。

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

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.