Rapid, low temperature and high yield synthesis of 67Ga and 111In radiocomplexes with new hexadentate bis(semicarbazone) and bis(thiosemicarbazone) chelators.
The synthesis of two new hexadentate potentially tetra-anionic acyclic chelators, an N 2O 4-donor bis(semicarbazone) ( H4bsc) and an N 2O 2S 2-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.