位点特异性放射性标记用于开发基于抗体或肽的放射治疗剂。尽管酪氨酸可用作肽和蛋白质位点特异性放射性标记的靶残基之一，但尚未建立酪氨酸特异性放射性标记方法。在本研究中，我们新设计并合成了一种新型双功能螯合剂TBD-DO3A，由三氮杂丁二烯（TBD）支架和金属螯合剂1,4,7,10-四氮杂环十二烷1,4,7-三乙酸（DO3A）组成）。 TBD-DO3A 与 Ac-Tyr-NHMe 缀合，然后进行 111In 标记，得到 [111In]In-Tyr-DO3A，其在小鼠血浆中表现出高度稳定性。然后，我们选择含酪氨酸的环肽c(RGDyK)作为模型配体并合成了[111In]In-RYD。 [111/natIn]In-RYD 对整合素 αvβ3 的体外结合特性与 [111/natIn]In-RKD（一种赖氨酸残基标记的对照化合物）相当。在使用 U87MG/PC-3 荷瘤小鼠进行的体内生物分布和 SPECT/CT 成像研究中，[111In]In-RYD 和 [111In]In-RKD 选择性积累，并在注射后 24 小时促进 U87MG 肿瘤可视化。这些结果表明 TBD-DO3A 具有作为肽和蛋白质的酪氨酸特异性放射性标记的双功能螯合剂的基本特性。

Site-specific radiolabeling is utilized for the development of antibody- or peptide-based radiotheranostic agents. Although tyrosine can be exploited as one of the target residues for site-specific radiolabeling of peptides and proteins, a tyrosine-specific radiolabeling method has not been established. In this study, we newly designed and synthesized a novel bifunctional chelating agent, TBD-DO3A, consisting of a triazabutadiene (TBD) scaffold and metal chelator, 1,4,7,10-tetraazacyclododecane 1,4,7-triacetic acid (DO3A). Conjugation of TBD-DO3A with Ac-Tyr-NHMe followed by 111In-labeling afforded [111In]In-Tyr-DO3A, which showed high-level stability in mouse plasma. Then, we selected the tyrosine-containing cyclic peptide c(RGDyK) as a model ligand and synthesized [111In]In-RYD. [111/natIn]In-RYD showed in vitro binding properties for integrin αvβ3 equivalent to those of [111/natIn]In-RKD, a lysine residue-labeled control compound. In in vivo biodistribution and SPECT/CT imaging studies using U87MG/PC-3 tumor-bearing mice, [111In]In-RYD and [111In]In-RKD were selectively accumulated and facilitated U87MG tumor visualization at 24 h postinjection. These results indicate that TBD-DO3A has fundamental properties as a bifunctional chelator for tyrosine-specific radiolabeling of peptides and proteins.