在线链和分支链结构之间比较碳酸盐无水酶-IX向的三功能放射性连接体
Kazuma Nakashima1, Takayoshi Ichinose1, Hiroyuki Watanabe1
1Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
与线性链版本相比,一个分支链放射性连接体 (In-DOTAGA-ALB-IS) 证明了优越的瘤向和减少脏吸收. 这表明分支设计可以提高CA-IX向放射性连体的有效性.
科学领域:
- 放射性药物化学 放射性药物化学
- 分子成像学分子成像学
- 癌症诊断 癌症诊断 癌症诊断
背景情况:
- 碳酸无水酶-IX (CA-IX) 是一种瘤生物标志物,在缺氧条件下过度表达.
- 专结合剂 (ALB) 可以通过延迟脏清除来改善放射性关节体瘤的传递.
- 三功能的放射性连接体结合了CA-IX向,化和蛋白结合.
研究的目的:
- 设计和评估具有线性和分支排列的新型CA-IX向三功能无线体.
- 为了比较线性 (IS-[111In]-DOTADG-ALB) 和分支 ([111In]-DOTAGA-ALB-IS) 放射性连体的体外和体内性能.
主要方法:
- 用印-111.11合成和放射性标记IS-DOTADG-ALB和DOTAGA-ALB-IS与印度-111.
- 在小鼠血中的体外稳定性测试.
- 细胞结合测定CA-IX和白蛋白亲和力.
- 在携带瘤的小鼠体内生物分布研究.
主要成果:
- 这两种放射性连体都成功合成,并显示出类似的CA-IX亲和力和血稳定性.
- 在DOTAGA-ALB-IS中表现出更高的白蛋白亲和力,导致血液保留和瘤积累的增加.
- 与线性IS-[111]In-DOTADG-ALB.IS相比,分支的[111]In-DOTAGA-ALB-IS表现出明显较低的吸收率,而线性IS-[111]In-DOTADG-ALB.IS则显示出明显较低的吸收率.
结论:
- DOTAGA-ALB-IS的分支链排列增强了瘤向性,并减少了CA-IX向性放射性链体在脏中的积累.
- 分支链设计有望开发用于癌症成像和治疗的改进放射性药物.
- 这项研究为通过结构修改优化放射性链体设计提供了基础.
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