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10P3Me:一种针对GPC3的质PET探头,用于皮下和正位体HCC成像

Gong Chen¹, Gangzhong Zhou², Xudong Sun¹

¹Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences & Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066, Lanzhou University, Lanzhou, Gansu 730000, P. R. China.

Journal of medicinal chemistry

|September 8, 2025

概括

一个新的分子探针10P3Me有效地准肝细胞癌 (HCC) 模型中的Glypican-3 (GPC3). 这种探测器对早期诊断和GPC3阳性HCC的分子成像显示出希望.

科学领域:

在瘤学瘤学.
分子成像学分子成像学
生物标志物开发生物标志物开发

背景情况:

肝细胞癌 (HCC) 是一个重要的全球健康问题.
早期诊断和向治疗对于改善HCC患者的治疗结果至关重要.
Glypican-3 (GPC3) 是HCC中过度表达的经过验证的生物标志物,使其成为分子探针的理想目标.

研究的目的:

开发和评估一种新的循环分子探针,10P3Me,用于准GPC3.3.
评估10P3Me在临床前HCC模型中的诊断和成像能力.

主要方法:

循环探针10P3Me.Me的合成和表征.
在体外结合亲和度测试以确定GPC3.3的解离常数 (Kd).
在GPC3-阳性和GPC3-低HCC模型中进行 pozitron发射断层扫描 (PET) 成像研究.
生物分布研究以评估瘤向性和选择性.

主要成果:

10P3Me对GPC3具有很高的结合亲和力 (Kd = 93.8 nM).
在GPC3阳性模型中,PET成像显示出显著的瘤向能力 (在1小时内峰值吸收5.61%ID/mL).
该探测器准确地定位了肝脏内病变在正位肝脏瘤模型中,瘤/肝脏吸收比为8.28,1小时.

结论:

10P3Me是一种有前途的分子探针,用于对GPC3阳性HCC的分子成像.
该探针的高亲和度和瘤选择性支持其在早期HCC诊断和监测方面的潜力.

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