Synthesis and characterization of a highly stable dendritic catechol-tripod bearing technetium-99m.
Fiche publication
Date publication
janvier 2010
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GALLANI Jean-Louis
Tous les auteurs :
Bertin A, Michou-Gallani AI, Steibel J, Gallani JL, Felder-Flesch D
Lien Pubmed
Résumé
The synthesis and preliminary biological tests (in vitro toxicity, in vitro stability) of new Tc(III)-radiolabelled dendro-chelates are presented. A dendritic (99m)Tc chelate 1 derived from a pre-organized tripodal tris-catecholamide exhibits a kinetic stability by far more important than its corresponding diethylenetriamine pentaacetic acid ( DTPA) homologue 2. This permitted an assessment of the real impact of the pre-organized tripodal structure on kinetic inertness ( and thus toxicity), an important issue to address when considering in vivo applications. Radiolabelling was performed using the stannous chloride reduction method; while DTPA-homologue 2 showed a high radiolabelling efficiency (96% radiolabelling yield after 30 min), tripodal complex 1 induced a 93% complexation yield after 45 min. In contrast, radiocomplex 1 derived from the most rigid and organized structure has a higher kinetic stability than 2. Indeed, while dissociation of 2 reached 50% after 1 h 30 min in physiological media like phosphate buffer saline (PBS) and bovine serum albumin (BSA), over 80% of 1 remained stable during the half-life of the radionucleide (6.02 h for (99m)Tc). Measurements of the cell leakage resulting from membrane damage of neuronal cells treated with increasing concentrations of dendritic ligand 16, together with pictures of treated neurons after staining, showed no detectable toxicity.
Référence
New J Chem. 2010;34(2):267-75.