Gallium and indium complexes with new hexadentate bis(semicarbazone) and bis(thiosemicarbazone) chelators

Abstract

The synthesis of two new hexadentate potentially tetra-anionic acyclic chelators, an N₂O₄-donor bis(semicarbazone) (H₄bsc) and an N₂O₂S₂-donor bis(thiosemicarbazone) (H₄btsc), is described. Coordination reactions of the ligands with gallium and indium precursors were investigated and yielded the complexes [Ga(Hbsc)] (1) and [In(Hbtsc)] (2), respectively. Ligands and complexes structures were confirmed by several techniques, including FTIR, NMR (¹H, ¹³C, COSY, HSQC), ESI(+)-MS and single crystal X-ray diffraction analysis. The radioactive congeners [⁶⁷Ga(Hbsc)] (1*) and [¹¹¹In(Hbtsc)] (2*) were also synthesized and their radiolabeling yield and radiochemical purity were certified by HPLC and ITLC analyses. Biodistribution assays in groups of CD-1 mice showed a high uptake of both radiocomplexes in liver and intestine where 1* presented higher retention. In vitro and in vivo assays revealed higher stability of 1* compared with 2*, namely in the blood. The results suggest that radiocomplex 1* is a candidate for further investigation as it could be prepared in high yields (>95%), at low temperature (20–25 °C) and at fast reaction time (15 min), which are very desirable synthesis conditions for potential new radiopharmaceuticals.