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一个新的Ga-标记的放射合成和评估,用于PD-L1-向PET成像

Fengsheng Zhang^{1,2,3,4,5,6,7}, Jindian Li^1,2,3,4,5,6, Xuwei Liu^1,2,3,4,5,6

¹Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.

Molecular pharmaceutics

|April 21, 2025

概括

一个新的68Ga-DOTA-CCC探针使得准确的正子发射断层扫描/计算机断层扫描 (PET/CT) 能够对编程死亡 1 (PD-L1) 表达进行成像. 这种新的工具显示出指导PD-L1向免疫治疗和改善患者反应率的希望.

科学领域:

核医学就是核医学.
放射化学放射化学是指辐射化学.
免疫治疗是一种免疫疗法.

背景情况:

编程死亡连接体1 (PD-L1) 向免疫疗法提供治疗效益,但反应率较低.
准确评估PD-L1表达对于指导有效的免疫治疗至关重要.
目前用于评估PD-L1表达的方法可能无法完全捕捉动态变化或瘤异质性.

研究的目的:

开发和评估一种新的68Ga标记的探头68Ga-DOTA-CCC,用于PD-L1.1.的正电子发射断层扫描/计算机断层扫描 (PET/CT) 成像.
评估探头在体内反映PD-L1表达水平的能力.
探索探测器在免疫治疗期间监测PD-L1动态中的实用性.

主要方法:

合成68Ga-DOTA-CCC通过对1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) 用CCC进行修改,并用68Ga.CCC进行标记.
在体外和体内评估探针的放射化学纯度,水友性 (log P),药理动力学,稳定性和生物安全性.
在临床前模型中进行MicroPET/CT成像,生物分布研究,以及瘤吸收与PD-L1表达的相关性.
在阿特佐利祖马布治疗期间监测PD-L1表达动态.

主要成果:

68Ga-DOTA-CCC成功合成了>99%的放射化学纯度和良好的水友性.
探针显示出快速的血液清除 (半衰期为16.1±0.5分钟) 和良好的稳定性.
68Ga-DOTA-CCC的瘤吸收与PD-L1表达水平正相关,通过细胞测定和微PET/CT成像证实了这一点.
在免疫治疗期间PD-L1表达的动态变化被成功可视化.

结论:

68Ga-DOTA-CCC是一种高效和特定的PET/CT成像探针,用于PD-L1.1.
探测器准确地反映了PD-L1表达水平及其动态变化.
这种新型成像剂具有指导PD-L1向免疫治疗和改善治疗结果的巨大潜力.

关键词:

在PD-L1中.免疫疗法免疫疗法微PET/CT成像成像技术放射性的放射性是一种放射性.

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