高效双功能去分化配体 3p-C-DEPA 用于靶向α放射性免疫治疗应用。
Efficient bifunctional decadentate ligand 3p-C-DEPA for targeted α-radioimmunotherapy applications.
机构信息
Chemistry Division, Biological, Chemical, and Physical Sciences Department, Illinois Institute of Technology, Chicago, Illinois, United States.
出版信息
Bioconjug Chem. 2011 Jun 15;22(6):1128-35. doi: 10.1021/bc100586y. Epub 2011 May 23.
Abstract
A new bifunctional ligand 3p-C-DEPA was synthesized and evaluated for use in targeted α-radioimmunotherapy. 3p-C-DEPA was efficiently prepared via regiospecific ring opening of an aziridinium ion and conjugated with trastuzumab. The 3p-C-DEPA-trastuzumab conjugate was extremely rapid in binding (205/6)Bi, and the corresponding (205/6)Bi-3p-C-DEPA-trastuzumab complex was stable in human serum. Biodistribution studies were performed to evaluate in vivo stability and tumor targeting of (205/6)Bi-3p-C-DEPA-trastuzumab conjugate in tumor bearing athymic mice. (205/6)Bi-3p-C-DEPA-trastuzumab conjugate displayed excellent in vivo stability and targeting as evidenced by low organ uptake and high tumor uptake. The results of the in vitro and in vivo studies indicate that 3p-C-DEPA is a promising chelator for radioimmunotherapy of (212)Bi and (213)Bi.
摘要
一种新的双功能配体 3p-C-DEPA 被合成并评估用于靶向α放射性免疫治疗。3p-C-DEPA 通过氮丙啶离子的区域特异性开环高效制备，并与曲妥珠单抗偶联。3p-C-DEPA-曲妥珠单抗缀合物与 205/6Bi 的结合非常迅速，相应的 205/6Bi-3p-C-DEPA-曲妥珠单抗复合物在人血清中稳定。进行了生物分布研究，以评估荷瘤裸鼠中 205/6Bi-3p-C-DEPA-曲妥珠单抗缀合物的体内稳定性和肿瘤靶向性。205/6Bi-3p-C-DEPA-曲妥珠单抗缀合物表现出优异的体内稳定性和靶向性，这表现为器官摄取低和肿瘤摄取高。体外和体内研究的结果表明，3p-C-DEPA 是 212Bi 和 213Bi 放射性免疫治疗的有前途的螯合剂。
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