title: Halogenated analogues of tamoxifen: synthesis, receptor assay, and inhibition of MCF7 cells.
abstract: This study was conducted to develop a ligand for imaging estrogen-receptor-positive breast tumors by positron emission tomography or single photon emission computed tomography. We synthesized fluoro and iodo analogues of tamoxifen, and these halogenated analogues produced greater affinity for binding to the receptor than tamoxifen. Values of the inhibition affinity constants were as follows: tamoxifen, 15,000 nM; fluoromethyl-N,N-diethyltamoxifen, 2500 nM for the cis isomer and 500 nM for the trans isomer; and iodomethyl-N,N-diethyltamoxifen, 1500 nM for the cis isomer and 1000 nM for the trans isomer. In studies of human MCF7 breast tumor cell growth, concentrations that inhibited tumor growth in 50% of the cases were as follows: tamoxifen, 11 microM; fluoromethyl-N,N-diethyltamoxifen, 4.5 and 11.8 microM for the cis and trans isomers, respectively; and iodomethyl-N,N-diethyltamoxifen, 2.4 and 6.3 microM for the cis and trans isomers, respectively. These studies suggest that both fluoro and iodo analogues of tamoxifen may be useful diagnostic compounds for predicting the response of estrogen-receptor-positive breast tumors to tamoxifen analogues used in chemotherapy.
authors.affiliation: Division of Diagnostic Imaging, University of Texas M.D. Anderson Cancer Center, Houston 77030.
authors.forename: D J
authors.initials: DJ
authors.lastname: Yang
authors.forename: T
authors.initials: T
authors.lastname: Tewson
authors.forename: W
authors.initials: W
authors.lastname: Tansey
authors.forename: L R
authors.initials: LR
authors.lastname: Kuang
authors.forename: G
authors.initials: G
authors.lastname: Reger
authors.forename: A
authors.initials: A
authors.lastname: Cherif
authors.forename: K C
authors.initials: KC
authors.lastname: Wright
authors.forename: R G
authors.initials: RG
authors.lastname: Moult
authors.forename: R S
authors.initials: RS
authors.lastname: Tilbury
authors.forename: K
authors.initials: K
authors.lastname: Chu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000737:chemistry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D011960:Receptors, Estrogen / Q000032:analysis*; D013552:Swine; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D011960:Receptors, Estrogen; D013629:Tamoxifen