[Abstract]Two decadentate acyclic chelators bearing four picolinic acid groups appended on either an ethylenediamine (H4TPAEN) or a trans-1,2-cyclohexyldiamine (H4TPADAC) unit were explored as candidates for lanthanum-based radiopharmaceutical development. The two chelators form ten-coordinated complexes with La3+ in the solid state, as evidenced by the corresponding X-ray structures and solution NMR studies. The La3+ complexes of TPAEN4– and TPADAC4– are characterized by high thermodynamic stability constants of log KLaL = 19.16(8) and 19.55(1), respectively. Kinetics studies indicate that the complexes dissociate following the acid-catalyzed and Cu2+-assisted pathways. Quantitative radiolabeling of both chelators with [135La]La3+ was achieved at pH ∼ 4–5 using straightforward protocols and low concentrations of the chelator (3 μM). Both in vitro and in vivo studies indicate that the [135La]La3+ complex of TPAEN4– is significantly more stable than the TPADAC4– analogue, with the former remaining intact and stable even after 60 min in vivo when injected to healthy mice