动态光散射用于评估Lu-DOTA-Trastuzumab中的聚合:放射性免疫治疗的质量控制方法
Huu Bao Nguyen1, Aran Kim2, Muhammad Zeeshan1
1Department of Molecular Medicine, Brain Korea 21 four KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, School of Medicine, Kyungpook National University, Daegu 41944, Korea.
Bioconjugate chemistry
|January 27, 2026
概括
使用卢-177 (Lu-177) 的放射性免疫疗法可能会导致抗体聚合,降低有效性. 动态光散射 (DLS) 监测和聚合物去除对于成功的放射性免疫治疗至关重要.
科学领域:
- 放射化学 放射化学是指辐射化学.
- 生物结合的生物结合
- 治疗抗体工程 治疗抗体工程
背景情况:
- 放射性免疫疗法 (RIT) 使用放射性标记抗体进行向癌症治疗.
- 高线性能量转移 (LET) 的同位素,如卢-177 (Lu-177) 可以诱导抗体聚合,损害稳定性和生物活性.
- 当前的质量控制方法可能无法检测由治疗性放射性同位素诱导的聚合.
研究的目的:
- 调查结合化学,放射标记条件和净化对[177Lu]Lu-DOTA-Trastuzumab的聚合的影响.
- 评估动态光散射 (DLS) 作为检测聚合的质量控制方法的有效性.
- 评估无聚合物[177Lu]Lu-DOTA-Trastuzumab在HER2阳性瘤中的治疗性能.
主要方法:
- [177Lu]Lu-DOTA-Trastuzumab的配方和特征使用不同的化剂与抗体比率和放射性水平.
- 通过动态光散射 (DLS) 进行聚合监测,并与传统方法 (SEC-HPLC,无线电-TLC) 进行比较.
- 在体内评估HER2特异性吸收,瘤积累和治疗疗效在HER2阳性小鼠模型中.
主要成果:
- 化剂与抗体比率的增加和放射性导致显著的聚合,未被SEC-HPLC或无线电TLC检测到.
- -177 (Lu-177) 诱导的聚合比铜-64 (Cu-64) 更多,与更高的放射性应力相关联.
- 聚合与HER2特异性吸收和瘤积累相反相关;无聚合物配方显示出优异的瘤生长抑制 (~65%).
结论:
- 动态光散射 (DLS) 是一种敏感且实用的工具,用于监测放射性免疫结合物的聚合.
- 聚合物形成是治疗放射性标记的一个关键问题,需要严格的质量控制.
- 确保无聚合物放射性免疫治疗剂的使用对于稳定的安全性,质量和治疗效果至关重要.
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