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Anti-HER2 monoclonal antibody based-radioimmunoconjugates: Assessment of the chelating agent influence
Bioorganic & Medicinal Chemistry ( IF 3.5 ) Pub Date : 2021-01-10 , DOI: 10.1016/j.bmc.2021.115996
Ana Cláudia Camargo Miranda 1 , Ana Claudia Ranucci Durante 2 , Leonardo Lima Fuscaldi 2 , Angélica Bueno Barbezan 3 , Cilene Rebouças de Lima 4 , Efrain Perini 3 , Elaine Bortoleti de Araújo 3
Affiliation  

In the present work, the radioimmunoconjugates 111In-DTPA-trastuzumab and 177Lu-DOTA-trastuzumab were evaluated regarding the influence of the chelating agents on the physical–chemical parameters and human epidermal growth factor receptor 2 (HER2) tumor cell binding. Data showed that both chelating agents, at predetermined molar ratios (antibody:chelator − 1:10 and 1:20), did not influence the immunoconjugates integrity, the radiolabeling process and the radiolabeled antibodies stability. However, differences were observed in the lipophilic feature between DOTA and DTPA radioimmunoconjugates and in the specific binding to SK-BR-3 tumor cells (HER2 positive). Therefore, this study showed the importance of assessing the influence of chelating agents and their molar ratios in the development process of radioimmunoconjugates.



中文翻译:

基于抗 HER2 单克隆抗体的放射免疫偶联物:螯合剂影响的评估

在目前的工作中,放射免疫偶联物111 In-DTPA-trastuzumab 和177Lu-DOTA-曲妥珠单抗评估螯合剂对理化参数和人表皮生长因子受体2(HER2)肿瘤细胞结合的影响。数据显示,预定摩尔比(抗体:螯合剂 - 1:10 和 1:20)的两种螯合剂不影响免疫偶联物的完整性、放射性标记过程和放射性标记抗体的稳定性。然而,在 DOTA 和 DTPA 放射免疫偶联物之间的亲脂性特征以及与 SK-BR-3 肿瘤细胞(HER2 阳性)的特异性结合方面观察到了差异。因此,本研究表明评估螯合剂及其摩尔比在放射免疫偶联物开发过程中的影响的重要性。

更新日期:2021-01-22
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