Coordination of Scandium(III) by an Octadentate Bispidine Ligand and Its Application to 44/47 Sc Radiolabeling

Scandium radioisotopes ( 43 Sc, 44 Sc, and 47 Sc) show strong promise for PET imaging and targeted radiotherapy. Their use requires the development of bifunctional chelators (BFCs) that can complex these metallic isotopes under mild conditions while maintaining a high in vivo stability. This study reports the synthesis and evaluation of two novel bispidine-based ligands for Sc(III) complexation, with a particular focus on L 1, which incorporates two picolinate substituents. The radiolabeling behavior, as well as the thermodynamic and kinetic properties of the corresponding Sc(III) complexes, were investigated. Ligand L 1 readily formed a stable 1:1 Sc(III) complex at room temperature, adopting a chair–chair conformation . Thermodynamic studies confirmed high stability (log K Sc L1 = 14.84, pSc = 10.7) and a notable preference for Sc(III) over Tb(III) (pTb = 7.8). L 1 enabled quantitative radiolabeling of 44 Sc at room temperature within 15 min (pH 6, M:L = 1:20). The complex is stable in human serum with no detectable decomplexation over 4 h and showed only partial decomplexation in hydroxyapatite challenge experiments. Successful radiolabeling with 47 Sc further highlighted its versatility. Together, these findings highlight the significant potential of the bispidine-based ligands. In particular, L 1 emerges as a promising platform for future developments in Sc-based radiopharmaceuticals and theragnostics.