To develop small molecular integrin‐selective luminescent imaging probes, we have prepared the binary dipicolinate (DPA) Tb^III dinuclear macrocyclic complex, Tb₂(cRGDfK‐ODO2A‐dimer) (DPA)₂^2– or complex I, and reference ligands and Tb^III complexes which were purified by HPLC and characterized by NMR, mass spectrometry and luminescence spectroscopy. Luminescence titrations of the structural and bonding model Tb₂(m‐ODO2A‐dimer)²⁺ complex by DPA^2– ion confirmed the molecular formula of the adduct was Tb₂(m‐ODO2A‐dimer)(DPA)₂^2–, and the first binary binding constant was determined to be log K₁ = 5.76. At pH 7.4, complex I showed 300 times luminescence enhancement at 544 nm (λ_ex = 278 nm) as compared to that without adding DPA, and was found to bind to α_vβ₃ integrin and human glioblastoma U87MG tumor cells in both specific and non‐specific modes, via luminescence spectroscopic and confocal cell imaging competition studies. This makes complex I and its future optimized derivatives potentially feasible for preclinical bioimaging applications, particularly in the time‐resolved mode.

中文翻译：

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环状RGD双核TbIII大环复合物作为肿瘤整合素选择性发光探针。

为了开发小分子整联蛋白选择性发光成像探针，我们准备了二吡啶甲酸（DPA）Tb ^III双核大环复合物，Tb ₂（cRGDfK-ODO2A-二聚体）（DPA）₂ ^2-或复合物I，以及参考配体和Tb通过HPLC纯化并通过NMR，质谱和发光光谱表征的^III配合物。用DPA ^2–离子滴定结构和键合模型Tb ₂（m ‐ODO2A‐dimer）²⁺络合物的发光滴定证实了加合物的分子式为Tb ₂（m ‐ODO2A‐dimer）（DPA）₂ ^2–，第一个二元结合常数确定为log  K ₁ = 5.76。在pH 7.4，复合物I显示300倍发光增强在544纳米（λ _EX相比于不添加DPA = 278纳米），并发现其结合到α _v β ₃整联和人成胶质细胞瘤U87MG肿瘤细胞的特异性和非特异性模式，通过发光光谱和共聚焦细胞成像竞争研究。这使得复杂的I及其未来优化的衍生物在临床前生物成像应用中尤其可行，特别是在时间分辨模式下。