Binding Characteristics and Biological Activity of 17α-[125I]Iodovinyl-11β-methoxyestradiol, an Estrogen Receptor-binding Radiopharmaceutical, in Human Breast Cancer Cells (MCF-7)

M. E. McManaway, E. M. Jagoda, W. C. Eckelman, S. M. Larson, B. E. Francis, R. E. Gibson, R. C. Reba, M. E. Lippman

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18 Scopus citations

Abstract

17α-[125I]Iodovinyl-11β-methoxyestradiol ([125I]MIVE2), a γ-emitting analogue of estradiol, previously shown to bind to rat uterine estradiol receptor, was studied to determine the binding characteristics and biological activity in human breast cancer cells. In vitro determination of receptor binding by dextran-coated charcoal assays indicates that [125I]MIVE2 binds specifically and with a high affinity to cytosolic estrogen receptors in the human breast cancer cell line, MCF-7. [3H]Estradiol binds to the receptor with approximately four times the affinity of [125I]MIVE2 (K(d) = 2.55 x 10-9 M for [125I]MIVE2; K(d) = 6.4 x 10-10 M for [3H]estradiol). Unlabeled MIVE2 produces estrogenic effects similar to those of estradiol such as progesterone receptor induction and increases in thymidine incorporation in MCF-7 cells in culture. Cytosolic progesterone receptor levels were elevated 2.8-fold over control levels by 6 x 10-9 M MIVE2. Stimulation of thymidine incorporation (approximately 300% above control levels) was observed after exposure to 1 x 10-9 M MIVE2. Preliminary data show receptor-mediated uptake by the uterus in biodistribution studies in athymic nude mice given injections of [125I] MIVE2 (32-34 μCi). At 4 h, uterus:blood ratios are 20.5 and target tissue:nontarget tissue ratios are 12.9. In light of the fact that this compound can be prepared with a high specific activity, [125I]MIVE2 may have potential as a radiotracer for imaging estrogen receptor-positive breast tumors or metastatic lesions in human breast cancer patients.

Original languageEnglish (US)
Pages (from-to)2386-2389
Number of pages4
JournalCancer Research
Volume46
Issue number5
StatePublished - May 1 1986

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    McManaway, M. E., Jagoda, E. M., Eckelman, W. C., Larson, S. M., Francis, B. E., Gibson, R. E., Reba, R. C., & Lippman, M. E. (1986). Binding Characteristics and Biological Activity of 17α-[125I]Iodovinyl-11β-methoxyestradiol, an Estrogen Receptor-binding Radiopharmaceutical, in Human Breast Cancer Cells (MCF-7). Cancer Research, 46(5), 2386-2389.