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

doi:10.1016/S0968-0896(02)00329-2

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 journal › Article

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 language	English (US)
Pages (from-to)	4075-4082
Number of pages	8
Journal	Bioorganic and Medicinal Chemistry
Volume	10
Issue number	12
DOIs	https://doi.org/10.1016/S0968-0896(02)00329-2
State	Published - Dec 1 2002

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Organic Chemistry
Drug Discovery
Pharmaceutical Science

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Lashley, M. R., Niedzinski, E. J., Rogers, J. M., Denison, M. S., & Nantz, M. H. (2002). Synthesis and estrogen receptor affinity of a 4-hydroxytamoxifen-labeled ligand for diagnostic imaging. Bioorganic and Medicinal Chemistry, 10(12), 4075-4082. https://doi.org/10.1016/S0968-0896(02)00329-2

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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.",

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AU - Niedzinski, Edmund J.

AU - Rogers, Jane M.

AU - Denison, Michael S.

AU - Nantz, Michael H.

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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.

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