Radiolabeling of monoclonal anti-CD105 with 177Lu for potential use in radioimmunotherapy
Radiolabeling of monoclonal anti-CD105 with 177Lu for potential use in radioimmunotherapy
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DOI：
10.1016/j.apradiso.2009.02.071
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发表时间：
2009-07-01
影响因子：
1.6
通讯作者：
Choi, Sun-Ju
中科院分区：
文献类型：
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作者：
Lee, So-Young;Hong, Young-Don;Choi, Sun-Ju
在本研究中，我们使用 Lu-177 与抗 CD105（内皮糖蛋白）单克隆抗体进行放射免疫结合，以靶向血管生成。 CD105 已被证明是比全内皮标记物更有用的标记物，可用于识别参与肿瘤血管生成的增殖内皮。我们使用半胱氨酸衍生物异硫氰酸苄基-DTPA (DTPA-NCS) 作为 BFCA，优化了 Lu-177 的抗 CD105 单克隆抗体标记。在最佳条件下，标记率大于99%。使用放射分析和生物分析技术（ITLC-SG、Cyclone 磷光成像仪、SDS-PAGE 和 ELISA）相结合来研究放射免疫缀合物的免疫活性。为了进行生物学评估，我们使用携带 Calu6 肺癌细胞异种移植物的小鼠进行了细胞结合测定和生物分布研究。注射后24小时肿瘤与血液的比率为11.16:1。总之，用于血管生成靶向的抗CD105单克隆抗体与Lu-177有效放射缀合。生物分布研究显示其在肿瘤组织中的积累具有高度特异性。这种放射免疫结合物适用于检测各种疾病中的血管生成位点和治疗肿瘤。 (C) 2009 Elsevier Ltd. 保留所有权利。
In this study, we carried out a radioimmunoconjugation using Lu-177 with anti-CD105 (endoglin) monoclonal antibody for an angiogenesis targeting. CD105 has been shown to be a more useful marker to identify proliferating endothelium involved in tumor angiogenesis than panendothelial markers. We optimized the labeling of the anti-CD105 monoclonal antibody with Lu-177 by using cysteine derivative isothiocyanatobenzyl-DTPA (DTPA-NCS) as BFCA. Under the optimal conditions, labeling yield was greater than 99%. Immunoactivity of the radioimmunoconjugate was investigated using combinations of radioanalytical and bioanalytical techniques (ITLC-SG, Cyclone phosphorimager, SDS-PAGE and ELISA). For the biological evaluations we carried out a cell binding assay and a biodistribution study using mice bearing Calu6 lung cancer cell xenografts. The tumor-to-blood ratio was 11.16:1 24h post-injection. In conclusion, the anti-CD105 monoclonal antibody for an angiogenesis targeting was effectively radioconjugated with Lu-177. And the biodistribution study showed a high specificity for accumulating in tumor tissues. This radjoimmunoconjugate is applicable to detect angiogenesis sites in various diseases and to treat tumors. (C) 2009 Elsevier Ltd. All rights reserved.