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在瘤中成像PD-L1的线性基PET标记剂

Lulu Zhang^1,2,3, Siqi Zhang², Jiang Wu¹

¹Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210008, China.

Molecular pharmaceutics

|June 27, 2023

概括

[64Cu]/[68Ga]HKP2201和[64Cu]/[68Ga]HKP2202的新型基放射追踪剂,在临床前癌症模型中有效地可视化了编程细胞死亡连接体1 (PD-L1),有助于评估治疗反应.

科学领域:

核医学是一种核医学.
放射化学放射化学是指辐射化学.
分子成像学分子成像学
癌症免疫疗法癌症免疫疗法

背景情况:

编程细胞死亡受体1 (PD-1) 和其连接体PD-L1是癌症中的关键免疫检查点.
定子发射断层扫描 (PET) 图像提供PD-L1表达的动态监测,用于预测治疗反应.
开发有针对性的放射追踪器对于有效的PD-L1可视化至关重要.

研究的目的:

为PD-L1成像合成和验证两种基于线性的新型放射追踪剂,即[64Cu]/[68Ga]HKP2201和[64Cu]/[68Ga]HKP2202.
在临床前癌症模型中评估这些标记物的诊断潜力.
为了比较新的跟踪器与现有的跟踪器的性能.

主要方法:

用铜-64 (64Cu) 和-68 (68Ga) 合成和放射性标记前体HKP2201 (来自CLP002) 和HKP2202 (二度化HKP2201).
在体外研究包括细胞吸收,结合测定和PD-L1表达细胞系的竞争性阻断 (B16F10,MC38).
使用PET成像和ex vivo生物分布在瘤携带小鼠模型中的体内研究.

主要成果:

对[64Cu]/[68Ga]HKP2201和[64Cu]/[68Ga]HKP2202.的放射性特征均为令人满意.
标志物表明与PD-L1具有特定的结合,具有度依赖的亲和力和可比的EC50值与WL12.
[64Cu]/[68Ga]HKP2202的瘤吸收率高于[64Cu]/[68Ga]HKP2201;64Cu-标记剂的瘤保留时间比68Ga-标记剂更长,68Ga-标记剂的肝脏积累率更低.

结论:

新型放射追踪器[64Cu]/[68Ga]HKP2201和[64Cu]/[68Ga]HKP2202对在临床前设置中可视化PD-L1状态具有前景.
这些标志物有潜力快速检测原发性和转移性瘤,包括肝癌.
需要进一步的临床评估,以确定它们在癌症诊断和治疗指南中的充分临床实用性.

关键词:

在PD-L1中.在PET成像中使用PET成像.[64Cu]/[68Ga]HKP2201 是一个 [64Cu]/[68Ga]HKP2202 的使用情况.免疫检查点阻断疗法阻断疗法线性酸是一种线性酸.

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