A Cyclic‐RGD Dinuclear TbIII Macrocyclic Complex as a Tumor Integrin‐Selective Luminescent Probe

• Published in: European journal of inorganic chemistry 2018-07, Vol.2018 (27), p.3270-3279
• Main Authors: Chang, C. Allen, Chia, Ju‐Chien, Lin, Syue‐Liang
• Format: Article
• Language: English
• Subjects: Coordination compounds; Cyclic RGD; Dimers; Feasibility studies; Imaging agents; Inorganic chemistry; Integrin‐selective binding; Lanthanides; Luminescence; Macrocyclic ligands; Mass spectrometry; Medical imaging; Molecular chains; NMR; Nuclear magnetic resonance; Tumors
• ISSN: 1434-1948; 1099-0682
• DOI: 10.1002/ejic.201800568

To develop small molecular integrin‐selective luminescent imaging probes, we have prepared the binary dipicolinate (DPA) TbIII dinuclear macrocyclic complex, Tb2(cRGDfK‐ODO2A‐dimer) (DPA)22– or complex I, and reference ligands and TbIII 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 DPA2– ion confirmed the molecular formula of the adduct was Tb2(m‐ODO2A‐dimer)(DPA)22–, 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 (λex = 278 nm) as compared to that without adding DPA, and was found to bind to αvβ3 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. The cyclic‐RGD dinuclear TbIII macrocyclic complex Tb2(cRGDfK‐ODO2A‐dimer)(DPA)22– at pH 7.4 showed 300 times luminescence (λex = 278 nm) enhancement at 544 nm as compared to that without DPA and was found to selectively bind to αvβ3 integrin and human glioblastoma U87MG tumor cells in fluorescence spectroscopic and confocal cell imaging competition studies, making it potentially feasible for practical bioimaging applications.