title: Synthesis and estrogen receptor affinity of a 4-hydroxytamoxifen-labeled ligand for diagnostic imaging.
abstract: A 10-step synthesis of a novel 4-hydroxytamoxifen-DTPA ligand (HOTam-DTPA) is reported. Tamoxifen and its primary metabolite 4-hydroxytamoxifen are common estrogen receptor ligands. Consequently, tamoxifen has found utility as the targeting component of various diagnostic agents for selective imaging of estrogen receptor-rich tissue, specifically breast cancer. An L-aspartic acid-derived DTPA analogue was attached to the ethyl side chain of 4-hydroxy-tamoxifen using N,N'-dimethylethylenediamine as a hydrophilic linker. A competitve estrogen receptor binding assay using [3H]-17beta-estradiol was performed to determine the effect of the ethyl side chain modification on estrogen receptor affinity. The results show that while the relative affinity of HOTam-DTPA for the estrogen receptor is approximately 10-fold lower than that of tamoxifen, it still remains a potent ligand at relatively low concentrations.
authors.affiliation: Department of Chemistry, University of California, Davis 95616, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Lashley
authors.forename: Edmund J
authors.initials: EJ
authors.lastname: Niedzinski
authors.forename: Jane M
authors.initials: JM
authors.lastname: Rogers
authors.forename: Michael S
authors.initials: MS
authors.lastname: Denison
authors.forename: Michael H
authors.initials: MH
authors.lastname: Nantz
mesh_terms: D000818:Animals; D002417:Cattle; D002614:Chelating Agents / Q000737:chemistry; D003952:Diagnostic Imaging / Q000379:methods*; D005260:Female; D008024:Ligands; D004369:Pentetic Acid / Q000737:chemistry; D011869:Radioligand Assay; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism; D014599:Uterus / Q000737:chemistry / Q000166:cytology
chemical_list: D002614:Chelating Agents; D008024:Ligands; D019275:Radiopharmaceuticals; D011960:Receptors, Estrogen; D013629:Tamoxifen; C016601:afimoxifene; D004369:Pentetic Acid