Synthesis, conjugation, and radiolabeling of a novel bifunctional chelating agent for 225Ac radioimmunotherapy applications
Synthesis, conjugation, and radiolabeling of a novel bifunctional chelating agent for 225Ac radioimmunotherapy applications
复制标题
DOI：
10.1021/bc990153f
复制
发表时间：
2000-07-01
影响因子：
4.7
通讯作者：
Brechbiel, MW
中科院分区：
文献类型：
--
作者：
Chappell, LL;Deal, KA;Brechbiel, MW
Ac-225（t(1/2) = 10 天）是一种替代 α 发射体，由于其许多有利的特性（例如半衰期和衰变模式）而被提议用于放射免疫疗法 (RIT)。限制 Ac-225 在 RIT 中使用的因素是缺乏体内应用可接受的稳定螯合物。本文描述了第一个报道的 (225)AC 双功能螯合物，已对其体内应用的稳定性进行了评估。报道了双功能螯合剂2-(4-异硫氰酸苄基)-1,4,7,10,13,16-六氮杂环十六烷-1,4,7,10,13,16-六乙酸(HEHA-NCS)的详细合成。该配体与三种单克隆抗体 CC49、T101 和 BL-3 缀合，螯合物与蛋白质的比率在 1.4 和 2 之间。这三种缀合物用 Ac-225 进行放射性标记，并对 [(225)AC]-BL-3-HEHA 缀合物进行血清稳定性研究。
Ac-225 (t(1/2) = 10 days) is an alternative alpha-emitter that has been proposed for radioimmunotherapy (RIT) due to its many favorable properties, such as half-life and mode of decay. The factor limiting use of Ac-225 in RIT is the lack of an acceptably stable chelate for in vivo applications. Herein is described the first reported bifunctional chelate for (225)AC that has been evaluated for stability for in vivo applications. The detailed synthesis of a bifunctional chelating agent 2-(4-isothiocyanatobenzyl)-1,4,7,10,13,16- hexaazacyclohexadecane-1,4,7,10,13,16-hexaacetic acid (HEHA-NCS) is reported. This ligand was conjugated to three monoclonal antibodies, CC49, T101, and BL-3 with chelate-to-protein ratios between 1.4 and 2. The three conjugates were radiolabeled with Ac-225, and serum stability study of the [(225)AC]-BL-3-HEHA conjugate was performed.