Synthesis and estrogen receptor affinity of a 4-hydroxytamoxifen-labeled ligand for diagnostic imaging

Matthew R. Lashley, Edmund J. Niedzinski, Jane M. Rogers, Michael S. Denison, Michael H. Nantz

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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]-17β-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 ∼10-fold lower than that of tamoxifen, it still remains a potent ligand at relatively low concentrations.

Original languageEnglish (US)
Pages (from-to)4075-4082
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume10
Issue number12
DOIs
StatePublished - Dec 1 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

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