Nonmacrocyclic Phosphonic‐Based Ligand for Theranostics Applications With ^44/47 Sc: From Complexation to Biodistribution

Scandium isotopes are attractive theranostic radiometals for personalized medicine. Several ligands have been evaluated, and among them the gold standard DOTA, there is still an unmet need to have ligands that bind Sc without elevated temperatures and able to be functionalized to targeting vectors (peptides, antibodies). The complexation of scandium with a pyridyl moiety functionalized by two amino(methyl)bis(methylphosphonic) acid (L _p ) has been evaluated. Complexation data have been obtained through free‐ion selective radiotracer extraction method, displaying the formation of a mononuclear Sc‐L _p complex with a conditional constant of log β _app  = 6.0 ± 0.2 at pH 5. Complexes were fully characterized by ⁴⁵ Sc NMR, ¹ H NMR, and ³¹ P NMR spectroscopy. Radiolabeling was performed at various temperatures in ammonium acetate buffer at pH 4.5, either with ⁴⁴ Sc eluted from a ⁴⁴ Ti generator or with ⁴⁷ Sc produced from a cyclotron. The radiolabeling yields were >98% at RT after 5 min of contact. The resulting [ ^44,47 Sc]Sc‐L _p complexes exhibited good stability in serum and against hydroxyapatite over 48 h. The [ ⁴⁷ Sc]Sc‐L _p complex injected in healthy mice ( n  = 3) showed a rapid clearance in kidneys. L _p ligand is thus a strong candidate to be further evaluated in vivo as a potential full theranostic radiopharmaceutical.