Radioisotopes of bismuth(III) are under evaluation in nuclear medicine as potential α-emitting therapeutic agents.¹ The energy emissions of α-particle decays are deposited over a very short distance (40-100 μm), resulting in a high linear energy transfer. The shorter path may also have the advantage of limiting toxicity to normal tissues adjacent to the tumour. 

The short half-life of the bismuth-212 (t_1/2 = 61 min) and bismuth-213 (t_1/2 = 46 min) radioisotopes limits their application. In addition, designing bismuth(III) chelators is challenging as they must exhibit fast complexation kinetics as well as high thermodynamic and kinetic stability. Nevertheless, the existence of stable isotopes of bismuth allows for investigations on the coordination chemistry of nonradioactive complexes. Bismuth generally assumes high coordination numbers (6-10) with irregular coordination geometries depending on the character of the polydentate ligand, the donor atoms and the solvent.

Tetraazacycloalkane chelators, such as cyclen-based derivatives, that contain four additional chelating groups by functionalisation of the cyclic nitrogen atoms are known for their affinity for heavy metal ions.² Bismuth complexes of the well-known H₄DOTA ligand have been reported but they display slow complexation kinetics.³

We will present the results of the incorporation of semicarbazone pendent arms into cyclen to offer a N₆O₂ coordination sphere to the metal centre. The nonradioactive bismuth(III) complex was synthesised and characterised. The ligand was radiolabelled with bismuth-213 at a range of concentrations and temperatures. The radiolabelled complex was stable in human serum in vitro out to 90 minutes and could represent an attractive alternative chelator for α-radiotherapy with bismuth radioisotopes.