Decadentate Acyclic Chelators for Lanthanum Radiopharmaceuticals.

Two decadentate acyclic chelators bearing four picolinic acid groups appended on either an ethylenediamine (HTPAEN) or a -1,2-cyclohexyldiamine (HTPADAC) unit were explored as candidates for lanthanum-based radiopharmaceutical development. The two chelators form ten-coordinated complexes with La in the solid state, as evidenced by the corresponding X-ray structures and solution NMR studies. The La complexes of TPAEN and TPADAC are characterized by high thermodynamic stability constants of log = 19.16(8) and 19.55(1), respectively. Kinetics studies indicate that the complexes dissociate following the acid-catalyzed and Cu-assisted pathways. Quantitative radiolabeling of both chelators with [La]La was achieved at pH ∼ 4-5 using straightforward protocols and low concentrations of the chelator (3 μM). Both and studies indicate that the [La]La complex of TPAEN is significantly more stable than the TPADAC analogue, with the former remaining intact and stable even after 60 min when injected to healthy mice.