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开发和应用的放射性干向纤维细胞与白蛋白结合部位的应用

Tongtong Wu¹, Zhicong Yang², Sufan Tang²

¹Affiliated Hospital of Southwest Medical University, , China.

Molecular cancer therapeutics

|April 3, 2025

概括

针对纤维细胞激活蛋白 (FAP) 的新型白蛋白结合放射性链体显示出癌症成像和治疗的前景. 177Lu-DOTA-ALB-02表现出优异的瘤保留和有利的生物分布,需要进一步的临床评估.

科学领域:

生物医学成像学生物医学成像学
放射化学放射化学是指辐射化学.
在瘤学瘤学.

背景情况:

纤维细胞激活蛋白 (FAP) 在与癌症相关的纤维细胞 (CAF) 上过度表达,具有治疗和诊断的目标.
当前FAP向剂的有限瘤保留阻碍了有效的晚期癌症诊断和放射性核酸治疗.

研究的目的:

合成和评估新的与蛋白结合的FAPI放射性质,以改善瘤保留和成像特性.
评估三种新的放射性连接体 (68Ga/177Lu-DOTA-ALB-01, 68Ga/177Lu-DOTA-ALB-02, 68Ga/177Lu-DOTA-ALB-03) 的体外稳定性,结合亲和力和体内生物分布.

主要方法:

三种与蛋白结合的FAPI放射性连体的合成.
在体外稳定性测试用盐水和血进行.
有约束力的亲和关系研究.
在临床前模型中使用68Ga和177Lu标签的体内生物分布和微SPECT成像.

主要成果:

所有合成的放射性体都表现出了卓越的体外稳定性和高的FAP结合亲和力.
177Lu-DOTA-ALB-02与其他放射性连接体相比,表现出更高的循环保留能力,包括177Lu-FAPI-46.
对于177Lu-DOTA-ALB-01和177Lu-DOTA-ALB-02,观察到持续的瘤积累,其中177Lu-DOTA-ALB-02实现了显著的瘤/非目标 (T/NT) 比率.

结论:

177Lu-DOTA-ALB-02由于其突出的瘤保留,具有有利的药理动力学和成像特性.
这种结合白蛋白的FAPI放射性连体是癌症诊断和放射性核素治疗中进一步临床研究的有希望的候选人.

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