title: Technetium- and rhenium-labeled progestins: synthesis, receptor binding and in vivo distribution of an 11 beta-substituted progestin labeled with technetium-99 and rhenium-186.
abstract: In an effort to develop radiopharmaceuticals useful for the diagnostic imaging of steroid receptor-positive breast tumors, we have radiolabeled an analog of the antiprogestin RU486 (mifepristone), modified to incorporate an N2S2 chelate system in the 11 beta-position, with 99Tc, 99mTc, and 186Re. For the 99Tc-labeled analogs (3), a syn pair and two individual antidiastereomers (linker methylene versus metal-oxo, relative to the N2S2 plane) were isolated. In competitive radiometric binding assays, the syn pair (3syn1,2) had affinity for the progesterone receptor that was 25% that of (promegestone) R5020 (or 161% that of progesterone), and the individual anti-diastereomers had affinities of 47% (3anti1) and 7% (3anti2) that of R5020 (or 303% and 45% that of progesterone). The specific-to-nonspecific binding ratio of the 99mTc (4) and 186Re (5) 11 beta-linked syn systems are 75/25 and 54/46, respectively. In vivo, conjugates 4 and 5 showed progesterone receptor-mediated uptake in rat uterus, but also high uptake in non-target tissues, presumably because of the high lipophilicity of the metal complexes. Modified systems may be useful in vivo as receptor-directed agents for diagnostic imaging or treatment of steroid receptor-positive tumors.
authors.affiliation: Department of Chemistry, University of Illinois, Urbana 61801.
authors.forename: J P
authors.initials: JP
authors.lastname: DiZio
authors.forename: C J
authors.initials: CJ
authors.lastname: Anderson
authors.forename: A
authors.initials: A
authors.lastname: Davison
authors.forename: G J
authors.initials: GJ
authors.lastname: Ehrhardt
authors.forename: K E
authors.initials: KE
authors.lastname: Carlson
authors.forename: M J
authors.initials: MJ
authors.lastname: Welch
authors.forename: J A
authors.initials: JA
authors.lastname: Katzenellenbogen
mesh_terms: D000818:Animals; D005260:Female; D007553:Isotope Labeling; D015735:Mifepristone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D011868:Radioisotopes / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D011980:Receptors, Progesterone / Q000378:metabolism*; D012211:Rhenium / Q000493:pharmacokinetics*; D013667:Technetium; D014018:Tissue Distribution; D014599:Uterus / Q000378:metabolism
chemical_list: D015609:Organotechnetium Compounds; D011868:Radioisotopes; D011980:Receptors, Progesterone; D015735:Mifepristone; D012211:Rhenium; D013667:Technetium