Asymmetrical Nitrido Tc-99m Heterocomplexes as Potential Imaging Agents for Benzodiazepine Receptors
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- 作者：Alessandra Boschi ; Licia Uccelli ; Adriano Duatti ; Cristina Bolzati ; Fiorenzo Refosco ; Francesco Tisato ; Romeo Romagnoli ; Pier Giovanni Baraldi ; Katia Varani ; and Pier Andrea Borea
- 刊名：Bioconjugate Chemistry
- 出版年：2003
- 出版时间：November 2003
- 年：2003
- 卷：14
- 期：6
- 页码：1279 - 1288
- 全文大小：116K
- 年卷期：v.14,no.6(November 2003)
- ISSN：1520-4812
文摘
The design, synthesis, and biological evaluation of nitrido technetium-99m complexes for imagingbenzodiazepine receptors are described. The design was performed by selecting the precursorbiologically active substrate desmethyldiazepam, and the reactive metal-containing fragment [99mTc(N)(PXP)]2+ (PXP = diphosphine ligand) as molecular building-blocks for assembling the structure ofthe 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 affordthe complexes [99mTc(N)(PXP)(L)] (L = BZ1, C1, C2). The chemical nature of the resulting Tc-99mradiopharmaceuticals was investigated using chromatographic methods, and by comparison with theanalogous complexes prepared with the long-lived isotope Tc-99g and characterized by spectroscopicand analytical methods. Results showed that the complexes [99mTc(N)(PXP)(L)] are neutral and possessan asymmetrical five-coordinated structure in which two different bidentate ligands, PXP and L, arecoordinated to the same Tc
N core. With the ligand H2BZ1, two isomers were obtained depending onthe 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 benzodiazepinereceptors was assessed through in vitro binding experiments on isolated rat's cerebral membranesusing the corresponding Tc-99g complexes.
N core. With the ligand H2BZ1, two isomers were obtained depending onthe 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 benzodiazepinereceptors was assessed through in vitro binding experiments on isolated rat's cerebral membranesusing the corresponding Tc-99g complexes.