title: Synthesis, characterization, and biological evaluation of technetium(III) complexes with tridentate/bidentate S,E,S/P,S coordination (E = O, N(CH(3)), S): a novel approach to robust technetium chelates suitable for linking the metal to biomolecules.
abstract: A novel type of mixed-ligand Tc(III) complexes, [Tc(SCH(2)CH(2)-E-CH(2)CH(2)S)(PR(2)S)] (E = S, N(CH(3)); PR(2)S = phosphinothiolate with R = aryl, alkyl) is described. These "3+2"-coordinated complexes can be prepared in a two-step reduction/substitution procedure via the appropriate chloro-containing oxotechnetium(V) complex [TcO(SES)Cl] [E=S, N(CH(3)]. Tc(III) compounds have been fully characterized both in solid and solution states and found to adopt the trigonal-bipyramidal coordination geometry. The equatorial trigonal plane is formed by three thiolate sulfur atoms, whereas the phosphorus of the bidentate P,S ligand and the neutral donor of the tridentate chelator occupy the apical positions. The (99)Tc(III) complexes have been proven to be identical with the (99m)Tc agents prepared at the no-carrier-added level by comparison of the corresponding UV/vis and radiometric HPLC profiles. Challenge experiments with glutathione clearly indicate that this tripeptide has no effect on the stability of the (99m)Tc complexes in solutions. Biodistribution studies have been carried out in rats at 5 and 120 min postinjection. The substituents at the bidentate P,S ligand significantly influence the biodistribution pattern. Remarkable differences are observed especially in brain, blood, lungs, and liver. All the complexes are able to penetrate the blood-brain barrier of rats and showed a relatively fast washout from the brain.
authors.affiliation: Forschungszentrum Rossendorf, Institut für Bioanorganische und Radiopharmazeutische Chemie, PF 510119, D-01314 Dresden, Germany. h.j.pietzsch@fz-rossendorf.de
authors.forename: Hans-Juergen
authors.initials: HJ
authors.lastname: Pietzsch
authors.forename: Sepp
authors.initials: S
authors.lastname: Seifert
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Syhre
authors.forename: Francesco
authors.initials: F
authors.lastname: Tisato
authors.forename: Fiorenzo
authors.initials: F
authors.lastname: Refosco
authors.forename: Peter
authors.initials: P
authors.lastname: Leibnitz
authors.forename: Hartmut
authors.initials: H
authors.lastname: Spies
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D002614:Chelating Agents / Q000032:analysis / Q000138:chemical synthesis / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents; D018360:Crystallography, X-Ray; D004355:Drug Stability; D005978:Glutathione / Q000494:pharmacology; D007267:Injections; D015394:Molecular Structure; D015609:Organotechnetium Compounds / Q000032:analysis / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D002614:Chelating Agents; D003432:Cross-Linking Reagents; D015609:Organotechnetium Compounds; D005978:Glutathione