Fluorescent gallium and indium bis(thiosemicarbazonates) and their radiolabelled analogues: synthesis, structures and cellular confocal fluorescence imaging investigations

• Published in: Dalton transactions : an international journal of inorganic chemistry 2011-06, Vol.40 (23), p.6238-6252
• Main Authors: Arrowsmith, Rory L, Waghorn, Philip A, Jones, Michael W, Bauman, Andreas, Brayshaw, Simon K, Hu, Zhiyuan, Kociok-Köhn, Gabriele, Mindt, Thomas L, Tyrrell, Rex M, Botchway, Stanley W, Dilworth, Jonathan R, Pascu, Sofia I
• Format: Article
• Language: English
• Subjects: Augers; Cell Line, Tumor; Confocal; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - toxicity; Crystallography, X-Ray; DNA Damage; Emittance; Fluorescence; Fluorescent Dyes - chemistry; Gallium - chemistry; Humans; Imaging; Indium; Indium - chemistry; Microscopy, Confocal; Molecular Conformation; Positron emission; Positron-Emission Tomography; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - chemistry; Radiopharmaceuticals - toxicity; Spectrophotometry, Ultraviolet; Tomography; Tomography, Emission-Computed, Single-Photon
• ISSN: 1477-9226; 1477-9234
• DOI: 10.1039/c1dt10126a

New fluorescent and biocompatible aromatic Ga(III)- and In(III)-bis(thiosemicarbazonato) complexes for dual mode optical and PET or SPECT molecular imaging have been synthesised via a synthetic method based on transmetallation reactions from Zn(II) precursors. Complexes have been fully characterised in the solid state by single crystal X-ray diffraction and in solution by spectroscopic methods (UV/Vis, fluorescence, (1)H and (13)C{(1)H} NMR). The bis(thiosemicarbazones) radiolabelled rapidly in high yields under mild conditions with (111)In (a gamma and Auger emitter for SPECT imaging and radiotherapy with t(1/2) = 2.8 d) and (68)Ga (a generator-available positron emitter for PET imaging with t(1/2) = 68 min). Cytotoxicity and biolocalisation studies using confocal fluorescence imaging and fluorescence lifetime imaging (FLIM) techniques have been used to study their in vitro activities and stabilities in HeLa and PC-3 cells to ascertain their suitability as synthetic scaffolds for future multimodality molecular imaging in cancer diagnosis and therapy. The observation that the indium complexes show certain nuclear uptake could be of relevance towards developing (111)In therapeutic agents based on Auger electron emission to induce DNA damage.