title: Asymmetrical nitrido tc-99m heterocomplexes as potential imaging agents for benzodiazepine receptors.
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 [(99m)Tc(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 H(2)BZ1, H(2)C1, and H(2)C2 (Figures 1 and 2) derived from desmethyldiazepam. In turn, these ligands were reacted with [(99m)Tc(N)(PXP)](2+) to afford the complexes [(99m)Tc(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 [(99m)Tc(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 Tc[triple bond]N core. With the ligand H(2)BZ1, two isomers were obtained depending on the syn or anti orientation of the pendant benzodiazepine group relative to the Tc[triple bond]N 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.
authors: Laboratory of Nuclear Medicine, Department of Clinical & Experimental Medicine, University of Ferrara, 44100 Ferrara, Italy.
authors: Alessandra
authors: A
authors: Boschi
authors: Licia
authors: L
authors: Uccelli
authors: Adriano
authors: A
authors: Duatti
authors: Cristina
authors: C
authors: Bolzati
authors: Fiorenzo
authors: F
authors: Refosco
authors: Francesco
authors: F
authors: Tisato
authors: Romeo
authors: R
authors: Romagnoli
authors: Pier Giovanni
authors: PG
authors: Baraldi
authors: Katia
authors: K
authors: Varani
authors: Pier Andrea
authors: PA
authors: Borea
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D015195:Drug Design; D004355:Drug Stability; D007202:Indicators and Reagents; D007553:Isotope Labeling; D008024:Ligands; D008297:Male; D015394:Molecular Structure; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D007202:Indicators and Reagents; D008024:Ligands; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D011963:Receptors, GABA-A