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 journalArticle

17 Citations (Scopus)

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

Fingerprint

Diagnostic Imaging
Estrogen Receptors
Pentetic Acid
Ligands
Imaging techniques
Tamoxifen
Metabolites
Aspartic Acid
Estradiol
Assays
afimoxifene
Tissue
Breast Neoplasms

ASJC Scopus subject areas

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

Cite this

Synthesis and estrogen receptor affinity of a 4-hydroxytamoxifen-labeled ligand for diagnostic imaging. / Lashley, Matthew R.; Niedzinski, Edmund J.; Rogers, Jane M.; Denison, Michael S.; Nantz, Michael H.

In: Bioorganic and Medicinal Chemistry, Vol. 10, No. 12, 01.12.2002, p. 4075-4082.

Research output: Contribution to journalArticle

Lashley, Matthew R. ; Niedzinski, Edmund J. ; Rogers, Jane M. ; Denison, Michael S. ; Nantz, Michael H. / Synthesis and estrogen receptor affinity of a 4-hydroxytamoxifen-labeled ligand for diagnostic imaging. In: Bioorganic and Medicinal Chemistry. 2002 ; Vol. 10, No. 12. pp. 4075-4082.
@article{4b7c03f9f88b414f834fcd61980cd5b7,
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]-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.",
author = "Lashley, {Matthew R.} and Niedzinski, {Edmund J.} and Rogers, {Jane M.} and Denison, {Michael S.} and Nantz, {Michael H.}",
year = "2002",
month = "12",
day = "1",
doi = "10.1016/S0968-0896(02)00329-2",
language = "English (US)",
volume = "10",
pages = "4075--4082",
journal = "Bioorganic and Medicinal Chemistry",
issn = "0968-0896",
publisher = "Elsevier Limited",
number = "12",

}

TY - JOUR

T1 - Synthesis and estrogen receptor affinity of a 4-hydroxytamoxifen-labeled ligand for diagnostic imaging

AU - Lashley, Matthew R.

AU - Niedzinski, Edmund J.

AU - Rogers, Jane M.

AU - Denison, Michael S.

AU - Nantz, Michael H.

PY - 2002/12/1

Y1 - 2002/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0036973248&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036973248&partnerID=8YFLogxK

U2 - 10.1016/S0968-0896(02)00329-2

DO - 10.1016/S0968-0896(02)00329-2

M3 - Article

C2 - 12413861

AN - SCOPUS:0036973248

VL - 10

SP - 4075

EP - 4082

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

SN - 0968-0896

IS - 12

ER -