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超分子化学能够在温和条件下对蛋白质进行放射性标记

Romane Vizier¹, Milou Boswinkel², Mathieu Moreau¹

¹Université Bourgogne Europe, CNRS, Institut de Chimie Moléculaire de l'Université de Bourgogne (ICMUB, UMR CNRS 6302), 9 Avenue Alain Savary, 21078 Dijon Cedex, France.

Molecular pharmaceutics

|October 13, 2025

概括

一种新的超分子化学方法使得核医学对抗体的轻度放射标记成为可能. 这种DOTA-cucurbit[7]uril前体允许有效和稳定的抗体-放射性金属复合体形成,以改善成像和治疗.

科学领域:

核医学是一种核医学.
超分子化学超分子化学
生物结合的生物结合

背景情况:

单克隆抗体对于核医学中的体内向至关重要.
由于恶劣的条件,传统的放射性标记方法可能会损害抗体完整性.
对于基于抗体的应用,需要温和高效的放射性标记技术.

研究的目的:

介绍一种基于超分子化学的新方法,用于抗体放射性标记.
开发一种用于用各种放射性核素进行放射性标记的多功能前体.
评估由此产生的放射性免疫结合物的稳定性和准效果.

主要方法:

合成DOTA-cucurbit[7]uril (DOTA-CB[7]) 前体的合成.
使用像111In.这样的放射性核素对DOTA-CB进行放射性标记[7].
通过超分子相互作用将放射标记DOTA-CB[7]与阿达曼坦-1-胺移植的抗HER2抗体 (trastuzumab) 进行特定位点的结合.
在体外和体内生物稳定性评估.
在HER2+瘤异种移植小鼠模型中进行SPECT/CT成像.

主要成果:

成功合成了DOTA-CB[7]前体.
在温和条件下,放射性标记DOTA-CB[7]对抗体进行有效和稳定的超分子结合.
放射性免疫结合物在体外和体内表现出高稳定性.
通过SPECT/CT成像证明HER2+瘤的有效向.
通过多种放射性核素 (111In, 68Ga, 89Zr, 177Lu, 225Ac) 成功进行放射性标记.

结论:

DOTA-CB[7] 能够对抗体进行高效和温和的超分子放射标记.
这种方法为传统的共价放射性标记提供了一种多功能替代方案.
这种方法适用于核医学应用中的热敏生物分子.
有可能改善基于抗体的诊断和治疗方法.

关键词:

在SPECT/CT测试中,抗体是对抗体的重要组成部分.生物结合生物结合库库尔比图里尔是一种.超分子化学超分子化学

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