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.

A key part of the development of metal based Positron Emission Tomography probes is the chelation of the radiometal. In this review the recent developments in the chelation of four positron emitting radiometals, ⁶⁸Ga, ⁶⁴Cu, ⁸⁹Zr and ⁴⁴Sc, are explored. The factors that effect the chelation of each radio metal and the ideal ligand system will be discussed with regards to high in vivo stability, complexation conditions, conjugation to targeting motifs and complexation kinetics. A series of cyclic, cross-bridged and acyclic ligands will be discussed, such as CP256 which forms stable complexes with ⁶⁸Ga under mild conditions and PCB-TE2A which has been shown to form a highly stable complex with ⁶⁴Cu. ⁸⁹Zr and ⁴⁴Sc have seen significant development in recent years with a number of chelates being applied to each metal - eight coordinate di-macrocyclic terephthalamide ligands were found to rapidly produce more stable complexes with ⁸⁹Zr than the widely used DFO.