Monitoring In Vivo Performances of Protein-Drug Conjugates Using Site-Selective Dual Radiolabeling and Ex Vivo Digital Imaging.
Monitoring In Vivo Performances of Protein-Drug Conjugates Using Site-Selective Dual Radiolabeling and Ex Vivo Digital Imaging.
复制标题
DOI：
10.1021/acs.jmedchem.2c00401
复制
发表时间：
2022-05-12
影响因子：
7.3
通讯作者：
Devel, Laurent
中科院分区：
文献类型：
--
作者：
Cahuzac, Heloise;Sallustrau, Antoine;Malgorn, Carole;Beau, Fabrice;Barbe, Peggy;Babin, Victor;Dubois, Steven;Palazzolo, Alberto;Thai, Robert;Correia, Isabelle;Lee, Ki Baek;Garcia-Argote, Sebastien;Lequin, Olivier;Keck, Mathilde;Nozach, Herve;Feuillastre, Sophie;Ge, Xin;Pieters, Gregory;Audisio, Davide;Devel, Laurent
在临床前模型中，开发和优化蛋白质-药物结合物需要准确测定蛋白质及其结合物的血浆和组织分布。为此，我们开发了一种基于双重放射性标记和体外数字成像的生物分析策略。通过酶反应和化学反应相结合的方法，我们得到了均一的双标记抗基质金属蛋白酶-14抗原结合片段，其中蛋白支架用碳14(14C)标记，药物用氚(3 H)标记。这些抗体-药物与不可切割或可切割连接物的结合物随后在体内进行了评估。通过将液体闪烁计数和体外双同位素放射成像相结合，不仅可以在循环阶段同时监测这两种成分，而且可以准确地定量它们在不同器官中的积累量。
In preclinical models, the development and optimization of protein–drug conjugates require accurate determination of the plasma and tissue profiles of both the protein and its conjugated drug. To this aim, we developed a bioanalytical strategy based on dual radiolabeling and ex vivo digital imaging. By combining enzymatic and chemical reactions, we obtained homogeneous dual-labeled anti-MMP-14 Fabs (antigen-binding fragments) conjugated to monomethyl auristatin E where the protein scaffold was labeled with carbon-14 (14C) and the conjugated drug with tritium (3H). These antibody–drug conjugates with either a noncleavable or a cleavable linker were then evaluated in vivo. By combining liquid scintillation counting and ex vivo dual-isotope radio-imaging, it was possible not only to monitor both components simultaneously during their circulation phase but also to quantify accurately their amount accumulated within the different organs.
登录
查看更多内容
DOI：
10.3390/ph13090245
发表时间：
2020-09-14
期刊：
Pharmaceuticals (Basel, Switzerland)
影响因子：
--
作者：
Joubert N;Beck A;Dumontet C;Denevault-Sabourin C
通讯作者：
Denevault-Sabourin C
DOI：
10.1016/b978-0-12-814395-7.00009-x
发表时间：
2020-01-01
期刊：
HANDBOOK OF RADIOACTIVITY ANALYSIS, VOL 2: RADIOANALYTICAL APPLICATIONS, 4TH EDITION
影响因子：
--
作者：
Barthe, Nicole;Maitrejean, Serge;Cardona, Ana
通讯作者：
Cardona, Ana
影响因子：
4.7
作者：
Dubowchik, GM;Firestone, RA;Trail, PA
通讯作者：
Trail, PA
影响因子：
9.3
作者：
Ilovich, Ohad;Qutaish, Mohammed;Bradley, Daniel P.
通讯作者：
Bradley, Daniel P.
影响因子：
5.3
作者：
Botzanowski, Thomas;Erb, Stephane;Cianferani, Sarah
通讯作者：
Cianferani, Sarah