放射性氟化纳米体PET示踪剂动态可视化体内差异Nectin4表达。

IF 6.8 1区医学 Q1 CHEMISTRY, MEDICINAL

Journal of Medicinal Chemistry Pub Date : 2025-10-02 DOI:10.1021/acs.jmedchem.5c01260

Dongye Zheng,Yong Huang,Chengze Li,Yanye Lu,Zhaoheng Xie,Qiushi Ren,Ying Liang,Xiangxi Meng

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引用次数: 0

摘要

Nectin4是多种癌症类型的潜在治疗靶点。为了开发nectin4的诊断性放射性示踪剂，从几个候选序列中选择了一种基于纳米体的PET示踪剂，并通过[18F]AlF放射性标记制备。在不同nectin4表达水平的细胞系和肿瘤模型中评估放射化学质量和示踪剂摄取。体外和体内研究表明，该示踪剂对nectin4具有特异性亲和力，在细胞系中的结合亲和力（KD）为6.77 nM。该示踪剂能够清晰地显示表达nectin4的病变，并通过动态PET成像和动力学分析表征其摄取谱和药代动力学行为。在肿瘤模型中也观察到PET信号强度与组织学上nectin4表达的相关性。因此，它可能有潜力成为临床应用的连接蛋白4示踪剂。

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A Radiofluorinated Nanobody PET Tracer to Dynamically Visualize Differential Nectin4 Expression In Vivo.

Nectin4 is a potential therapeutic target for multiple cancer types. To develop a diagnostic radiotracer for nectin4, a nanobody-based PET tracer was selected from several candidate sequences and prepared via [18F]AlF radiolabeling. The radiochemical quality was assessed, and tracer uptake was evaluated in cell lines and tumor models with varying nectin4 expression levels. In vitro and in vivo studies showed that the tracer exhibited a specific affinity for nectin4, with a binding affinity (KD) of 6.77 nM in cell lines. The tracer enabled clear visualization of nectin4-expressing lesions, and its uptake profile and pharmacokinetic behavior were characterized using dynamic PET imaging and kinetic analysis. A correlation between PET signal intensity and histological nectin4 expression was also observed in tumor models. Thus, it may have the potential to become a nectin4 tracer for clinical applications.

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来源期刊

Journal of Medicinal Chemistry 医学-医药化学

CiteScore

4.00

自引率

11.00%

发文量

804

审稿时长

1.9 months

期刊介绍： The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents. The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.