Pretargeting offers a way to enhance target specificity while reducing off-target radiation dose to healthy tissue during payload delivery. We recently reported the development of an ¹⁸F-based pretargeting strategy predicated on the inverse electron demand Diels–Alder reaction as well as the use of this approach to visualize pancreatic tumor tissue in vivo as early as 1 h postinjection. Herein, we report a comprehensive structure: pharmacokinetic relationship study of a library of 25 novel radioligands that aims to identify radiotracers with optimal pharmacokinetic and dosimetric properties. This investigation revealed key relationships between molecular structure and in vivo behavior and produced two lead candidates exhibiting rapid tumor targeting with high target-to-background activity concentration ratios at early time points. We believe this knowledge to be of high value for the design and clinical translation of next-generation pretargeting agents for the diagnosis and treatment of disease.

中文翻译：

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探索用于预靶向放射性配体优化的结构参数

预靶向提供了一种在降低有效载荷输送过程中对健康组织的脱靶辐射剂量的同时增强靶标特异性的方法。我们最近报告了¹⁸基于F的预靶向策略基于逆电子需求Diels–Alder反应以及这种方法的使用，可在注射后1 h内可视化体内胰腺肿瘤组织。在这里，我们报告一个全面的结构：25个新型放射性配体的库的药代动力学关系研究，旨在确定具有最佳药代动力学和剂量学特性的放射性示踪剂。这项研究揭示了分子结构与体内行为之间的关键关系，并产生了两个主要候选物，这些候选物在早期时间点以快速的肿瘤靶向性和较高的靶与背景活性浓度比。我们相信这些知识对于设计和临床翻译用于疾病诊断和治疗的下一代靶向药物具有很高的价值。