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

The synthesis of two new hexadentate potentially tetra-anionic acyclic chelators, an N2O4-donor bis(semicarbazone) (H(4)bsc) and an N2O2S2-donor bis(thiosemicarbazone) (H(4)btsc), 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 (H-1, C-13, COSY, HSQC), ESI(+)-MS and single crystal X-ray diffraction analysis. The radioactive congeners [Ga-67(Hbsc)] (1*) and [In-111(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 degrees C) and at fast reaction time (15 min), which are very desirable synthesis conditions for potential new radiopharmaceuticals.

Automated summary

Two new hexadentate potentially tetra-anionic acyclic chelators were successfully synthesized, characterized, and labeled with radioactive isotopes for biodistribution studies. The results showed high uptake of both radiocomplexes in liver and intestine, with radiocomplex 1* exhibiting higher retention. In vitro and in vivo assays revealed that radiocomplex 1* displayed higher stability compared to 2*, particularly in the blood.