[ nat Y/ 90 Y]Yttrium and [ nat Lu/ 177 Lu]Lutetium Complexation by Rigid H 4 OCTAPA Derivatives. Effect of Ligand Topology

We present a detailed investigation on the coordination chemistry of [ nat/90 Y]Y 3+ and [ nat/177 Lu]Lu 3+ with the new acyclic chelator H 4 CHX OITAPA. This octadentate chelator forms nine‐coordinated Y 3+ and Lu 3+ complexes thanks to the coordination of a water molecule, as demonstrated by the X‐ray structure of [Y(H CHX OITAPA)(H 2 O)] and 1 H, 13 C, and 89 Y NMR studies in solution. These complexes display slightly higher thermodynamic stabilities compared with those of the known H 4 CHX OCTAPA and H 4 OCTAPA chelators, reaching log K YL and log K LuL values of 21.24(5) and 21.96(1), respectively. Kinetic studies indicate that these complexes dissociate mainly through the spontaneous and proton‐assisted pathways at pH 7.4. The chelator can be readily radiolabeled with [ 90 Y]Y 3+ and [ 177 Lu]Lu 3+ at room temperature in 10 min. The radio‐complexes are stable in human serum at 37 °C, in contrast with the analogues of the known H 4 CHX OCTAPA and H 4 OCTAPA chelators, which experience significant dissociation under these conditions. Thus, the H 4 CHX OITAPA chelator represents the most promising candidate among the H 4 OCTAPA family for the development of 90 Y‐ and 177 Lu‐based radiopharmaceuticals.