N-Heterocyclic Carbenes as Ligands to ¹⁹⁸Au(I)-Radiolabeled Compounds: A New Platform for Radiopharmaceutical Design

The radionuclide ¹⁹⁸Au, with a half-life of 2.7 days, emits γ radiation ideal for diagnostic purposes and generates β^- particles suitable for effective cancer radiotherapy, making it a perfect nuclide for "theranostics". However, the application of coordination compounds of Au(I)/Au(III) in medicine is limited by their instability in vivo. Here, we explore N-heterocyclic carbene (NHC) organometallic chemistry to stabilize ¹⁹⁸Au(I) in radiopharmaceuticals. Thus, Au(I) NHC compounds featuring different scaffolds were selected for ¹⁹⁸Au radiolabeling. Eventually, two compounds featuring imidazole (AuNHC-1) and theophylline (AuTMX₂) scaffolds were successfully radiolabeled (radiochemical purity = 92.9% and 40.2%, respectively). Instead, two peptidic Au(I) benzimidazolylidene derivatives, capable of blood-brain barrier translocation in vitro, were subjected to ligand exchange reactions under the applied radiolabeling conditions. The obtained proof-of-concept results showed that NHCs are suitable ligands to achieve isotope exchange in Au(I) complexes. Overall, our work reveals the still untapped potential of organometallic chemistry in radiopharmaceutical design.