The design, synthesis, and biological evaluation of nitrido technetium-99m complexes for imaging benzodiazepine receptors are described. The design was performed by selecting the precursor biologically active substrate desmethyldiazepam, and the reactive metal-containing fragment [99mTc(N)(PXP)]2+ (PXP = diphosphine ligand) as molecular building-blocks for assembling the structure of the final radiopharmaceuticals through the application of the so-called 'bifunctional' and 'integrated' approaches. This required the synthesis of the ligands H2BZ1, H2C1, and H2C2 (Figures 1 and 2) derived from desmethyldiazepam. In turn, these ligands were reacted with [99mTc(N)(PXP)]2+ to afford the complexes [99mTc(N)(PXP)(L)] (L = BZ1, C1, C2). The chemical nature of the resulting Tc-99m radiopharmaceuticals was investigated using chromatographic methods, and by comparison with the analogous complexes prepared with the long-lived isotope Tc-99g and characterized by spectroscopic and analytical methods. Results showed that the complexes [99mTc(N)(PXP)(L)] are neutral and possess an asymmetrical five-coordinated structure in which two different bidentate ligands, PXP and L, are coordinated to the same TcN core. With the ligand H2BZ1, two isomers were obtained depending on the syn or anti orientation of the pendant benzodiazepine group relative to the TcN multiple bond. Biodistribution studies of Tc-99m complexes were carried out in rats, and affinity for benzodiazepine receptors was assessed through in vitro binding experiments on isolated rat's cerebral membranes using the corresponding Tc-99g complexes.
Asymmetrical nitrido tc-99m heterocomplexes as potential imaging agents for benzodiazepine receptors
BOSCHI, Alessandra;UCCELLI, Licia;DUATTI, Adriano;ROMAGNOLI, Romeo;VARANI, Katia;
2003
Abstract
The design, synthesis, and biological evaluation of nitrido technetium-99m complexes for imaging benzodiazepine receptors are described. The design was performed by selecting the precursor biologically active substrate desmethyldiazepam, and the reactive metal-containing fragment [99mTc(N)(PXP)]2+ (PXP = diphosphine ligand) as molecular building-blocks for assembling the structure of the final radiopharmaceuticals through the application of the so-called 'bifunctional' and 'integrated' approaches. This required the synthesis of the ligands H2BZ1, H2C1, and H2C2 (Figures 1 and 2) derived from desmethyldiazepam. In turn, these ligands were reacted with [99mTc(N)(PXP)]2+ to afford the complexes [99mTc(N)(PXP)(L)] (L = BZ1, C1, C2). The chemical nature of the resulting Tc-99m radiopharmaceuticals was investigated using chromatographic methods, and by comparison with the analogous complexes prepared with the long-lived isotope Tc-99g and characterized by spectroscopic and analytical methods. Results showed that the complexes [99mTc(N)(PXP)(L)] are neutral and possess an asymmetrical five-coordinated structure in which two different bidentate ligands, PXP and L, are coordinated to the same TcN core. With the ligand H2BZ1, two isomers were obtained depending on the syn or anti orientation of the pendant benzodiazepine group relative to the TcN multiple bond. Biodistribution studies of Tc-99m complexes were carried out in rats, and affinity for benzodiazepine receptors was assessed through in vitro binding experiments on isolated rat's cerebral membranes using the corresponding Tc-99g complexes.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
