TY - JOUR
T1 - N-Heterocyclic Carbenes as Ligands to 198Au(I)-Radiolabeled Compounds: A New Platform for Radiopharmaceutical Design
AU - Spreckelmeyer, Sarah
AU - Thomas, Sophie R.
AU - Schuderer, Franziska
AU - Pinto, Catarina I. G.
AU - Querino, Ana Luiza de Andrade
AU - Böhm, Felix A.
AU - Park, Mihyun
AU - Geppert, Christopher
AU - Gorges, Christian
AU - Mendes, Filipa
AU - Casini, Angela
PY - 2025/8/28
Y1 - 2025/8/28
N2 - 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 (AuTMX
2) 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.
AB - 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 (AuTMX
2) 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.
UR - https://doi.org/10.1021/acs.jmedchem.5c01073
U2 - 10.1021/acs.jmedchem.5c01073
DO - 10.1021/acs.jmedchem.5c01073
M3 - Article
SN - 0022-2623
VL - 68
SP - 17516
EP - 17526
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 16
ER -