title: Stability versus reactivity of "3+1" mixed-ligand technetium-99m complexes in vitro and in vivo.
abstract: "3+1" technetium-99m mixed-ligand complexes as relevant to the development of a third generation of 99mTc radiopharmaceuticals were investigated in vivo and in vitro in the blood of rats. Surprisingly, in whole blood the complexes, which proved to be stable in saline, PBS of pH 7.4 and in plasma, were converted into two radioactive, more hydrophilic metabolites. Small structural differences in the complex molecule have a profound influence on the rate of metabolism of the complexes. To obtain an understanding of this unexpected reactivity, transchelation reactions with glutathione (GSH) were hypothesized and this hypothesis substantiated by challenge experiments carried out with a series of 99mTc and analogous rhenium complexes and GSH. In vitro studies in human plasma, whole blood and erythrocytes also revealed conversion of the complexes, though, at a much slower rate. Structural parameters influencing the stability of the complexes and consequences for the radiopharmaceutical design are discussed.
authors.affiliation: Institut für Bioanorganische und Radiopharmazeutische Chemie, Forschungszentrum Rossendorf, PF 510 119, D-01314 Dresden, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Syhre
authors.forename: S
authors.initials: S
authors.lastname: Seifert
authors.forename: H
authors.initials: H
authors.lastname: Spies
authors.forename: A
authors.initials: A
authors.lastname: Gupta
authors.forename: B
authors.initials: B
authors.lastname: Johannsen
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013056:Spectrophotometry, Ultraviolet; D017556:Technetium Compounds / Q000737:chemistry*
chemical_list: D017556:Technetium Compounds; D005978:Glutathione