Fiche publication
Date publication
août 2026
Journal
International journal of molecular sciences
Auteurs
Membres identifiés du Cancéropôle Est :
Pr KARCHER Gilles
Tous les auteurs :
Dhimen A, Assfeld X, Karcher G, Collet C, Acherar S
Lien Pubmed
Résumé
The development of hybrid bifunctional chelators (BFCs) capable of efficiently coordinating both diagnostic and therapeutic radionuclides remains a major challenge in theranostic radiopharmaceutical design. Herein, two novel hybrid NOTA-derived chelators, and , were developed from the previously reported BFC to improve the coordination of Lu while preserving efficient AlF labeling. Both ligands were successfully synthesized and fully characterized by NMR and mass spectrometry analyses. Their coordination properties toward {AlF} and Lu were thoroughly investigated by molecular modeling, non-radioactive complexation, and radiolabeling studies. Both chelators efficiently formed AlF complexes, exhibiting high complexation yields and successful AlF radiolabeling with good stability. In contrast, only efficiently coordinated Lu, whereas failed to form stable Lu complexes under both non-radioactive and radiolabeling conditions. Optimized radiolabeling of with Lu afforded high radiochemical conversion, consistent with the molecular modeling predictions. These results demonstrate that the spatial positioning of the additional donor arm, rather than linker elongation alone, is a key determinant for efficient coordination of larger trivalent radiometals. Thus, emerged as the most promising candidate for further development of targeted radiopharmaceuticals based on the AlF/Lu theranostic approach.
Mots clés
Al18F/177Lu theranostic, bifunctional chelator, coordination chemistry, hybrid chelator, molecular modeling, radiolabeling
Référence
Int J Mol Sci. 2026 08 19;27(16):
