| 15898735 |
Fernandes C, Correia JD, Gano L, Santos I, Seifert S, Syhre R, Bergmann R, Spies H: Dramatic effect of the tridentate ligand on the stability of 99mTC "3 + 1" oxo complexes bearing arylpiperazine derivatives. Bioconjug Chem. 2005 May-Jun;16(3):660-8.
Mixed-ligand model complexes of general formula [(99m) Tc (O)(kappa (3)-PNX)(kappa (1)-SPh))] [X = O (1a), S (2a)] were prepared in a one-step procedure from [(99m) TcO (4)(-)] using stannous chloride as reducing agent. Stability studies and challenge experiments with glutathione showed that complex 2a presented promising features for pursuing animal studies. The activity in the brain (% dose injected/organ) at 5 min (0.14% +/- 0.03) and 120 min (0.11% +/- 0.02) pi encouraged the synthesis of several mixed-ligand "3 + 1" oxo complexes of general formula [M (O)(kappa (3)-PNS)(kappa (1)-SL))] (M = (99m) Tc, 3a-6a, Re, 3-6), in which the tridentate ligand is the heterofunctionalized phosphine 2-(diphenylphosphanyl)-N-(2-thioethyl) benzamide (PNS) and the co-ligands are different arylpiperazine derivatives (HSL1-HSL4). The (99m) Tc complexes have been characterized by comparison of their retention times in the HPLC chromatogram (gamma-detection) with the retention times of the analogous Re complexes (UV detection at 254 nm). The (99m) Tc complexes, obtained with radiochemical purity higher than 95%, after HPLC purification, are stable in saline, 0.01 M PBS (pH 7.4), rat plasma (4 h, 37 degrees C), and glutathione (10 mM solutions, 2h, 37 degrees C). Binding affinity and selectivity for 5-HT (1A) receptors (relative to the 5-HT (2A) receptor) were determined, complex 5 demonstrating the best values (IC (50) for the 5-HT (1A) 2.35 +/- 0.02 nM; competitor 5-HT (2A) 372 +/- 11 nM). Biodistribution and stability studies in mice indicated a preferred hepatobiliary excretion, a high in vivo stability, but a poor brain uptake. |
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