Evaluation of Dynamic Light Scattering as an Effective Quality Control Method for Aggregates in Radiolabeled Antibodies.

Autor: Nguyen HB; Department 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., Park H; Division of Applied RI, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea., Lim JE; Department 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., Nguyen TT; Department 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., Kim HH; Department 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., Kim K; Department 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., Kim JY; Division of Applied RI, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea., Lee KC; Division of Applied RI, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea., Yoo J; Department 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.
Jazyk: angličtina
Zdroj: Journal of medicinal chemistry [J Med Chem] 2024 Dec 16. Date of Electronic Publication: 2024 Dec 16.
DOI: 10.1021/acs.jmedchem.4c02344
Abstrakt: 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 [ 64 Cu]CuCl 2 , 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.
Databáze: MEDLINE