99m Tc标记循环针对PD-L1作为一种新型核成像探测器
Guillermina Ferro-Flores1, Blanca Ocampo-García1, Pedro Cruz-Nova1
1Department of Radioactive Materials, Instituto Nacional de Investigaciones Nucleares, Ocoyoacac 52750, Mexico.
Pharmaceutics
|December 23, 2023
概括
开发了一种新型的技术-99m标记的抑制剂,针对编程死亡配体1 (PD-L1),用于SPECT成像. 这种放射性药物在临床前模型和患者中成功检测到PD-L1阳性瘤,显示出癌症诊断的潜力.
科学领域:
- 核医学是一种核医学.
- 在瘤学瘤学.
- 放射性药物化学 放射性药物化学
背景情况:
- 癌症疗法越来越多地准瘤微环境免疫抑制,特别是编程死亡-1 (PD-1) 途径.
- 癌细胞通过表达PD-1连接体 (PD-L1) 来逃避免疫监测,PD-L1抑制了免疫T细胞.
- 准确的PD-L1表达的成像对于指导向免疫疗法至关重要.
研究的目的:
- 设计,合成和评估一种针对PD-L1 (Tc-iPD-L1) 的Tc标记循环抑制剂.
- 评估Tc-iPD-L1作为一种用于成像PD-L1表达在癌症中的SPECT放射性药物.
- 为了研究99mTc-iPD-L1.1的临床前和初始临床效用.
主要方法:
- 分子对接 (AutoDock) 用于对iPD-L1联体的亲和度计算.
- 化学合成涉及将一个循环与一种氨酸胺衍生物结合起来,然后进行99mTc标签.
- 进行了放射化学纯度 (Radio-HPLC),稳定性 (HPLC),特异性 (SDS-PAGE),细胞吸收,瘤携带小鼠的生物分布以及人类SPECT成像研究.
主要成果:
- 该iPD-L1连接体表现出高结合亲和力 (-6.7 kcal/mol),并以97%的纯度合成.
- 准备的Tc-iPD-L1具有90%以上的放射性化学纯度,并且在人体血清中表现出极好的稳定性 (>90%在24小时内).
- 试验室和体内研究显示了特定的PD-L1识别,高瘤吸收 (1小时6.98±0.89%的ID/g) 和快速清除.
- 在患有恶性黑色素瘤的患者中,SPECT成像成功可视化了PD-L1阳性病变.
结论:
- 99mTc-iPD-L1是一种有前途的SPECT放射性药物,用于成像PD-L1表达.
- 开发的药物在检测PD-L1阳性瘤方面表现出良好的临床前和临床初始性能.
- 需要进一步的剂量测量和临床研究来确定Tc-iPD-L1/SPECT成像的灵敏度和特异性.
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