title: Synthesis of novel progestin-rhenium conjugates as potential ligands for the progesterone receptor.
abstract: To assist in the development of technetium-based radiopharmaceuticals that are useful for the diagnostic imaging of steroid receptor-positive breast tumors, we have synthesized a series of small-sized metal chelates according to 'n + 1' mixed-ligand, thioether-carbonyl and organometallic designs. In these preliminary investigations, rhenium was used as a model for the radioactive technetium. The metal chelates contain the rhenium metal in several oxidation states, being + 5, + 3, and + 1, and they were attached to 21-substituted progesterone derivatives. A competitive receptor-binding assay (rat uterine cytosol, 0 degrees C) was used to determine the binding affinity of these conjugates for the progesterone receptor. The highest affinity of 9% (RU5020 = 100%) was obtained with a '3 + 1' mixed-ligand complex, containing a NMe group as the central donor atom in the tridentate ligand part. This value reflects a relative binding affinity of 75% compared with the parent steroid progesterone.
authors.affiliation: Institut für Bioanorganische und Radiopharmazeutische Chemie, Dresden, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Wüst
authors.forename: M B
authors.initials: MB
authors.lastname: Skaddan
authors.forename: P
authors.initials: P
authors.lastname: Leibnitz
authors.forename: H
authors.initials: H
authors.lastname: Spies
authors.forename: J A
authors.initials: JA
authors.lastname: Katzenellenbogen
authors.forename: B
authors.initials: B
authors.lastname: Johannsen
mesh_terms: D018360:Crystallography, X-Ray; D008024:Ligands; D011372:Progestins / Q000737:chemistry* / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism*; D012211:Rhenium / Q000737:chemistry* / Q000378:metabolism; D013057:Spectrum Analysis
chemical_list: D008024:Ligands; D011372:Progestins; D011980:Receptors, Progesterone; D012211:Rhenium