title: Design and synthesis of functionalized cyclopentadienyl tricarbonylmetal complexes for technetium-94m PET imaging of estrogen receptors.
abstract: Cyclopentadienyl tricarbonylmetal (CpTM, M = Re, (94m)Tc) complexes, some based on a typical nonsteroidal estrogen, were prepared with the aim of developing technetium- and rhenium-labeled imaging agents for estrogen receptor (ER) positive breast tumors. CpT[(94m)Tc] compounds with simple cyclopentadienyl substituents were first synthesized using a modified double ligand transfer reaction. The in vivo biodistribution of one of these CpT[(94m)Tc] complexes was determined by tissue dissection and microPET imaging. Novel C-ring substituted analogues of cyclofenil, a nonsteroidal compound known to bind the ER, were also prepared, and their ER binding was measured. Because of their low ER affinity, however, labeling and imaging studies of these compounds were not pursued. It is notable that the highest ER binding analogue, a CpTRe cyclofenil derivative, could be synthesized from the corresponding ferrocenyl cyclofenil analogue by the double ligand transfer reaction. This further demonstrates the versatility of the double ligand transfer reaction and indicates that the synthesis of technetium and rhenium radiolabeled agents for breast tumor imaging and therapy is also likely to be successful.
authors.affiliation: Division of Radiological Sciences, Washington University School of Medicine, 510 S. Kingshighway, Campus Box 8225, St. Louis, Missouri 63110, USA.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Bigott
authors.forename: Ephraim
authors.initials: E
authors.lastname: Parent
authors.forename: Leonard G
authors.initials: LG
authors.lastname: Luyt
authors.forename: John A
authors.initials: JA
authors.lastname: Katzenellenbogen
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Welch
mesh_terms: D000818:Animals; D003517:Cyclopentanes / Q000138:chemical synthesis / Q000493:pharmacokinetics; D015195:Drug Design; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011960:Receptors, Estrogen / Q000032:analysis*; D014018:Tissue Distribution
chemical_list: D003517:Cyclopentanes; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D011960:Receptors, Estrogen