title: Novel oxorhenium and oxotechnetium MO(NS)(S)2 complexes in the development of 5-HT1A receptor imaging agents.
abstract: The [NS][S](2) mixed-ligand system was applied to synthesize oxorhenium and oxotechnetium complexes of the general formula MO(o-CH(3)OC(6)H(4)N(CH(2)CH(2))(2)NCH(2)CH(2)S)(p-CH(3)C(6)H(4)S)(2) (M=Re in 1, M=(99)Tc in 2, and M=(99m)Tc in 3). The bidentate [NS] ligand includes the 1-(2-methoxyphenyl)piperazine moiety which is a fragment of the true 5-HT(1A) antagonist WAY 100635. The oxorhenium complex 1 was prepared by a ligand exchange reaction using ReOCl(3)(PPh(3))(2) as precursor while [Bu(4)N][(99)TcOCl(4)] and (99)Tc-gluconate were used as precursors in the synthesis of the oxotechnetium-99 complex 2. Both complexes were characterized by elemental analysis and spectroscopic methods. Crystallographic analysis of 1 showed that the rhenium coordination geometry is trigonal bipyramidal. The basal plane of the trigonal bipyramid is defined by the oxo group and two sulphur atoms, one belonging to the [NS] ligand and the other to an aromatic thiol, while the apical positions are occupied by the nitrogen of the [NS] ligand and the sulphur of the second aromatic thiol. The oxotechnetium-99 complex 2 has almost identical unit cell parameters to those of the oxorhenium complex 1 indicating, in combination with the other analytical data, that the complexes are isostructural. The binding affinity of the oxorhenium complex 1 for the 5-HT(1A) receptor subtype was determined in rat brain hippocampal preparations (IC(50)=106 nM). The oxotechnetium-99m complex 3 was prepared by a ligand exchange reaction using (99m)Tc-glucoheptonate as the precursor. Its structure was established by comparative HPLC studies using the oxotechnetium-99 complex 2 as a reference. Complex 3 was administered by intravenous injection in rats. At 2 min post injection, 0.153% of the injected dose per gram of tissue was measured in rat brain.
authors.affiliation: Institute of Radioisotopes-Radiodiagnostic Products, National Centre for Scientific Research 'Demokritos', 15310 Ag. Paraskevi, Athens, Greece.
authors.forename: Charalambos
authors.initials: C
authors.lastname: Tsoukalas
authors.forename: Ioannis
authors.initials: I
authors.lastname: Pirmettis
authors.forename: George
authors.initials: G
authors.lastname: Patsis
authors.forename: Maria
authors.initials: M
authors.lastname: Pelecanou
authors.forename: Katalin
authors.initials: K
authors.lastname: Bodo
authors.forename: Catherine P
authors.initials: CP
authors.lastname: Raptopoulou
authors.forename: Aris
authors.initials: A
authors.lastname: Terzis
authors.forename: Minas
authors.initials: M
authors.lastname: Papadopoulos
authors.forename: Efstratios
authors.initials: E
authors.lastname: Chiotellis
mesh_terms: D000818:Animals; D003287:Contrast Media; D018360:Crystallography, X-Ray; D003952:Diagnostic Imaging / Q000379:methods; D006624:Hippocampus / Q000737:chemistry / Q000000981:diagnostic imaging / Q000378:metabolism; D008024:Ligands; D008297:Male; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics; D011868:Radioisotopes / Q000008:administration & dosage; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000032:analysis*; D044263:Receptors, Serotonin, 5-HT1; D012211:Rhenium / Q000008:administration & dosage / Q000493:pharmacokinetics; D013667:Technetium / Q000008:administration & dosage / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D003287:Contrast Media; D008024:Ligands; D009942:Organometallic Compounds; D011868:Radioisotopes; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012211:Rhenium; D013667:Technetium