Htrica: Versatile Macrocyclic Chelator for [Ac]Ac and [Tb]Tb Theranostics.

Htrica is a nonadentate chelating ligand intended for coordinating large radiometal ions, such as those used in nuclear medicine. This chelator, featuring a triaza-18-crown-6 macrocycle with three pendant carboxylic acid functional groups, was synthesized and characterized. Complementary nuclear magnetic resonance (NMR) spectroscopy and high-resolution electrospray-ionization mass spectroscopy (HR-ESI-MS) studies were used to explore the coordination of Htrica with metal ions such as La, Y (as a model for Tb, and Lu at the bulk scale. Thermodynamic solution studies provided valuable insights, highlighting robust metal complexation of Htrica with La, Tb, and Lu, with the most noteworthy log value observed for Tb (log = 17.08), followed by La (log = 16.64) and Lu (log = 16.25). Concentration-dependent radiolabeling studies with [Ac]Ac, [Tb]Tb, and [Tb]Tb demonstrated rapid complexation (5-30 min) under mild conditions (pH 6-7, 25 °C). Importantly, the radiolabeled complexes exhibited stability during incubation in human serum for one-half-life of the corresponding radiometal. Thus, Htrica emerges as a valuable chelator, demonstrating its potential to coordinate the theranostic couple [Ac]Ac/[Tb]Tb as well as the powerful terbium quartet ([Tb]Tb) with efficiency and stability.