Article Dans Une Revue Chemistry - A European Journal Année : 2025

[natY/90Y]Yttrium and [natLu/177Lu]Lutetium Complexation by Rigid H4OCTAPA Derivatives. Effect of Ligand Topology

Fátima Lucio-Martínez
Rocío Uzal-Varela
David Esteban-Gómez
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Gyula Tircsó
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Résumé

We present a detailed investigation on the coordination chemistry of [nat/90Y]Y3+ and [nat/177Lu]Lu3+ with the new acyclic chelator H4CHXOITAPA. This octadentate chelator forms nine-coordinated Y3+ and Lu3+ complexes thanks to the coordination of a water molecule, as demonstrated by the X-ray structure of [Y(HCHXOITAPA)(H2O)] and 1H, 13C, and 89Y NMR studies in solution. These complexes display slightly higher thermodynamic stabilities compared with those of the known H4CHXOCTAPA and H4OCTAPA chelators, reaching log KYL and log KLuL 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 [90Y]Y3+ and [177Lu]Lu3+ at room temperature in 10 min. The radio-complexes are stable in human serum at 37 degrees C, in contrast with the analogues of the known H4CHXOCTAPA and H4OCTAPA chelators, which experience significant dissociation under these conditions. Thus, the H4CHXOITAPA chelator represents the most promising candidate among the H4OCTAPA family for the development of 90Y- and 177Lu-based radiopharmaceuticals.

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hal-05104871 , version 1 (10-06-2025)

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Fátima Lucio-Martínez, Balazs Szilagyi, Rocío Uzal-Varela, Paulo Perez-Lourido, David Esteban-Gómez, et al.. [natY/90Y]Yttrium and [natLu/177Lu]Lutetium Complexation by Rigid H4OCTAPA Derivatives. Effect of Ligand Topology. Chemistry - A European Journal, 2025, 31 (28), pp.e202500799. ⟨10.1002/chem.202500799⟩. ⟨hal-05104871⟩
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