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

• Published in: Angewandte Chemie 2022-02, Vol.134 (7), p.n/a
• Main Authors: Whetter, Jennifer N., Vaughn, Brett A., Koller, Angus J., Boros, Eszter
• Format: Article
• Language: English
• Subjects: Chemistry; Fluorine; Fluorine isotopes; Image quality; Imaging; In vivo methods and tests; Isotopes; Positron emission; Positron emission tomography; Radiation therapy; Radiochemistry; Radioisotopes; Radiopharmaceuticals; Robustness; Scandium; Tomography
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202114203

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. 18F, however, does not have a suitable therapeutic isotopologue. Here, we demonstrate that the formation of [18F][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 [18F][Sc−F] tracer indicates excellent in vivo stability and produces exquisite PET image quality, rendering the 18F/47Sc isotope pair an unusual, yet chemically matched theranostic pair with excellent potential for clinical translation. We report a two‐step, one‐pot water‐compatible and high‐yielding radiofluorination approach by the displacement of a labile, inner‐sphere water of a seven‐coordinate Sc chelate with a 18F− ion to form the first fully inert and water‐compatible Sc–18F ternary coordination complex. The corresponding complex is fully in vivo compatible and can be the diagnostic PET imaging partner to the corresponding 47Sc‐labeled endoradiotherapeutic.