Speltri Giorgia, Badrane Ilham, Napolitano Rebecca, Boschi Alessandra, Uccelli Licia, Filippi Luca, Guidoboni Massimo, Brunelli Matteo, Lancia Federica, Martini Petra, Iudicello Antonella, Cittanti Corrado, Bartolomei Mirco, Urso Luca
Department of Chemical, Pharmaceutical, and Agricultural Sciences, University of Ferrara, Via L. Borsari, 46-44121, Ferrara, Italy.
Department of Translational Medicine, University of Ferrara, Ferrara, Italy.
Mol Diagn Ther. 2025 Jun 5. doi: 10.1007/s40291-025-00786-6.
Nectin cell adhesion molecule 4 (Nectin-4) is specifically overexpressed in most cancers of epithelial origin but downregulated in normal tissue, representing an ideal target for positron emission tomography imaging. The development of positron emission tomography imaging probes targeting Nectin-4 has gained significant attention in recent years, especially after the approval in December 2019 by the US Food and Drug Administration of enfortumab vedotin-an antibody drug conjugate targeting Nectin-4-in patients with locally advanced or metastatic bladder cancer. This article aims to comprehensively review original research articles discussing preclinical development or early translational clinical applications of radiolabeled probes targeting Nectin-4. The main radioactive compounds investigated belong to two classes, antibody-based radiopharmaceuticals and peptide-drug conjugates, in particular novel bicyclic peptides. While monoclonal antibody-based probes have demonstrated theranostic potential in preclinical studies, their clinical application has been hindered by their slow pharmacokinetic properties. However, peptide-based positron emission tomography/computed tomography tracers offer several advantages, such as ease of handling in synthesis, a more favorable biodistribution, and lower immunogenicity and have been tested in preliminary clinical experiences.
NECTIN细胞黏附分子4（Nectin-4）在大多数上皮源性癌症中特异性高表达，但在正常组织中表达下调，是正电子发射断层扫描成像的理想靶点。近年来，靶向Nectin-4的正电子发射断层扫描成像探针的研发备受关注，尤其是在2019年12月美国食品药品监督管理局批准恩诺单抗（一种靶向Nectin-4的抗体药物偶联物）用于局部晚期或转移性膀胱癌患者之后。本文旨在全面综述讨论靶向Nectin-4的放射性标记探针的临床前开发或早期转化临床应用的原创研究文章。所研究的主要放射性化合物分为两类，基于抗体的放射性药物和肽-药物偶联物，特别是新型双环肽。虽然基于单克隆抗体的探针在临床前研究中已显示出诊疗潜力，但其临床应用受到其缓慢药代动力学特性的阻碍。然而，基于肽的正电子发射断层扫描/计算机断层扫描示踪剂具有几个优点，如合成操作简便、生物分布更有利、免疫原性较低，并已在初步临床经验中进行了测试。
