An Unusual Pair: Facile Formation and In Vivo Validation of Robust Sc-¹⁸ F Ternary Complexes for Molecular Imaging

Fluorine-18 remains the most widely clinically utilized radionuclide globally for positron emission tomography (PET). The emergence of therapeutic isotopes for the management of disease has produced a pronounced interest in matched, theranostic isotope pairs that can be employed in tandem for the diagnosis and stratification of patients for subsequent radiotherapy. ¹⁸ F, however, does not have a suitable therapeutic isotopologue. Here, we demonstrate that the formation of [¹⁸ F][Sc-F] ternary complexes is feasible under mild, aqueous conditions, producing chemically robust radiopharmaceuticals in high radiochemical yield and specific activity. A corresponding in vivo study with a cancer-targeting [¹⁸ F][Sc-F] tracer indicates excellent in vivo stability and produces exquisite PET image quality, rendering the ¹⁸ F/⁴⁷ Sc isotope pair an unusual, yet chemically matched theranostic pair with excellent potential for clinical translation.