Selective Chelation of the Exotic Meitner-Auger Emitter Mercury-197 m/g with Sulfur-Rich Macrocyclic Ligands: Towards the Future of Theranostic Radiopharmaceuticals.

Mercury-197 m/g are a promising pair of radioactive isomers for incorporation into a theranostic as they can be used as a diagnostic agent using SPECT imaging and a therapeutic via Meitner-Auger electron emissions. However, the current absence of ligands able to stably coordinate Hg to a tumour-targeting vector precludes their use in vivo. To address this, we report herein a series of sulfur-rich chelators capable of incorporating Hg into a radiopharmaceutical. 1,4,7,10-Tetrathia-13-azacyclopentadecane (NS ) and its derivatives, (2-(1,4,7,10-tetrathia-13-azacyclopentadecan-13-yl)acetic acid (NS -CA) and N-benzyl-2-(1,4,7,10-tetrathia-13-azacyclopentadecan-13-yl)acetamide (NS -BA), were designed, synthesized and analyzed for their ability to coordinate Hg through a combination of theoretical (DFT) and experimental coordination chemistry studies (NMR and mass spectrometry) as well as Hg radiolabeling studies and in vitro stability assays. The development of stable ligands for Hg reported herein is extremely impactful as it would enable their use for in vivo imaging and therapy, leading to personalized treatments for cancer.