Octadentate Picolinic Acid‐Based Bispidine Ligand for Radiometal Ions

Abstract

Abstract The synthesis of the octadentate bispidine ligand bearing two picolinic acid pendant arms (H 2 bispa 2 ), and its coordination chemistry with radionuclides relevant for nuclear medicine, namely indium(III) ( 111 In), lutetium(III) ( 177 Lu), and lanthanum(III) (as surrogate for 225 Ac), are reported. The non‐radioactive metal complexes of the N 6 O 2 ‐type bispa ligand were characterized by 1 H and 13 C NMR spectroscopy, elemental analysis, mass spectrometry and single‐crystal X‐ray analysis. Experimental structural data, computational analysis, complex stabilities determined by potentiometric titration, and “radiostabilities” determined by competition studies in the presence of human serum reveal complex stabilities of H 2 bispa 2 comparable to those of the macrocyclic “gold standard” DOTA. After an incubation time of 1 day, 86 and 87 % of [ 177 Lu(bispa 2 )] + and [ 177 Lu(DOTA)] − , respectively, remain intact. Importantly, unlike DOTA, H 2 bispa 2 is radiolabeled quantitatively with 111 In III and 225 Ac III under ambient conditions, which is an essential aspect when working with heat‐sensitive antibodies as targeting vectors. In the case of 111 In III , room temperature radiolabeling of H 2 bispa 2 yields molar activities as high as 70 MBq nmol −1 within 10 minutes. These are promising results for radiopharmaceutical applications of H 2 bispa 2 .