Radiolabeled antibodies are promising for targeted cancer imaging, but their structural integrity may suffer during bioconjugation and radiolabeling, leading to undetected aggregation. This study evaluates dynamic light scattering (DLS) as a complementary method to size-exclusion high-performance liquid chromatography (SEC-HPLC) for detecting aggregation in radiolabeled antibodies. Trastuzumab was conjugated with a NOTA bifunctional chelator at various ratios, radiolabeled with [⁶⁴Cu]CuCl₂, and analyzed by using DLS and SEC-HPLC before and after purification. DLS revealed significant aggregation during preparation, undetected by SEC-HPLC, and showed reduced aggregates following purification. Tumor-targeting efficacy correlated with intact antibody content, with Pearson’s correlations of 0.71 (PET imaging) and 0.75 (biodistribution) in NIH3T6.7 tumor-bearing mice. The findings suggest DLS as a vital quality control tool, offering enhanced detection of antibody aggregation. By adopting DLS, the bioactivity of radiolabeled antibodies can be better predicted, potentially improving the reliability and effectiveness of these radiopharmaceuticals in clinical settings.

中文翻译：

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动态光散射作为放射性标记抗体中聚集体的有效质量控制方法的评价


放射性标记抗体有望用于靶向癌症成像，但其结构完整性在生物偶联和放射性标记过程中可能会受到影响，导致未检测到的聚集。本研究评估了动态光散射 （DLS） 作为尺寸排阻高效液相色谱 （SEC-HPLC） 的补充方法，用于检测放射性标记抗体中的聚集。曲妥珠单抗与不同比例的 NOTA 双功能螯合剂偶联，用 [⁶⁴Cu]CuCl₂ 放射性标记，并在纯化前后使用 DLS 和 SEC-HPLC 进行分析。DLS 显示制备过程中有显著的聚集，SEC-HPLC 未检测到，纯化后聚集体减少。肿瘤靶向效力与完整抗体含量相关，在 NIH3T6.7 荷瘤小鼠中，Pearson 的相关性为 0.71 （PET 成像） 和 0.75 （生物分布）。研究结果表明 DLS 是一种重要的质量控制工具，可提供增强的抗体聚集检测。通过采用 DLS，可以更好地预测放射性标记抗体的生物活性，从而有可能提高这些放射性药物在临床环境中的可靠性和有效性。