Advertisement

Potential Breast Tumor Imaging Agents: Fluorotamoxifen and Derivatives

  • David J. Yang
  • Ali M. Emran
  • Wayne Tansey
  • Kenneth C. Wright
  • Li-Ren Kuang
  • Gregg Reger
  • Roy Tilbury
  • Sidney Wallace
  • E. Edmund Kim

Abstract

This study is aimed at developing a ligand to be used for imaging estrogen receptor positive breast tumors by Positron Emission Tomography (PET). We describe the synthesis of fluorotamoxifen analogs with the fluorine atom positioned on the aliphatic side chain of tamoxifen and the measurement of the in vitro binding of fluorotamoxifens to estrogen receptors. N,N-Diethylfluorotamoxifen was prepared from the tosyl ester of the corresponding hydroxy derivative. 18F-Labeled N,N-diethylfluoromethyltamoxifen was prepared in 60% yield. These studies indicate that fluorinated tamoxifens have high affinity for estrogen receptors and can be labeled with 18F, thus reflecting a potential for use in imaging estrogen receptors by PET.

Keywords

Positron Emission Tomography Estrogen Receptor High Performance Liquid Chromatography Trans Isomer Aliphatic Side Chain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    J.L. Wittliff. Steroid-hormone receptors in breast cancer, Cancer Res. 53: 630 (1984).Google Scholar
  2. 2.
    W.L. McGuire, K.B. Horowitz, O.H. Pearson and A. Segaloff. Current status of estrogen and progesterone receptors in breast cancer, Cancer 39: 2934 (1977).Google Scholar
  3. 3.
    M.D. Fernandez, J.I. Burn, P.D. Sauven, G. Parmar, J.O. White and L. Myatt. Activated estrogen receptors in breast cancer and response to endocrine therapy, Eur. J. Cancer Clin. Oncol. 20: 41 (1984).PubMedCrossRefGoogle Scholar
  4. 4.
    M.A. Mintun, M.J. Welch, B.A. Siegel, C.J. Mathias, J.W. Brodack, A.H. McGuire and J.A. Katzenellenbogen. Breast cancer: PET imaging of estrogen receptors, Radiology 169: 45 (1988).Google Scholar
  5. K. Hamacher, H.H. Coenen, G. Stöcklin. Efficient sterospecific synthesis of no-carrier-added 1-18Ffluoro-2-deoxy-D-glucose using aminopolyether supported nucleophilic substitution, J. Nucl. Med. 27(2):235 (1986).Google Scholar
  6. 6.
    A.B. Foster, R. McCague, A. Seago, G. Leclercq, S. Stoessel and F. Roy. Modification of the basic side chain in tamoxifen: effects on microsomal metabolism and in vitro biological activity, Anticancer Drug Design. 1: 245 (1986).Google Scholar
  7. W.C. Still, M. Kahn and A. Mitra. Rapid chromatographic technique for preparative separations with moderate resolution, J. Org. Chem. 43, 2923 (1978).Google Scholar
  8. A.B. Foster, M. Jarman, 0-T Leung, R. McCague, G. Leclercq and N-Devleeschouwer. Hydroxy derivatives of tamoxifen, J. Med. Chem. 28:1491 (1985).Google Scholar
  9. J.H. Fishman. Stabilization of estradiol-receptor complexes by elimination of cytosolic factors, Biochem. Biophys. Res. Commun. 110:713 (1983).Google Scholar
  10. R. McCague, G. Leclercq and V.C. Jordan Nonisomerizable analogs of (Z) and (E)-4-hydroxytamoxifen. Synthesis and endocrinological properties of substituted diphenylbenzocycloheptenes, J. Med. Chem. 31:1285 (1988).Google Scholar
  11. 11.
    O.H. Lowry, N.J. Rosebrough. A.L. Farr, and R.J. Randall. Protein measurement with the Folin phenol reagent, J. Biol. Chem. 193: 265 (1951).PubMedGoogle Scholar
  12. T. Mosmann, Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assays, J. Immunol. Methods 65:55 (1983).Google Scholar
  13. J. Shani, A. Gazit, T. Livshitz and S. Biran. Synthesis and receptor binding affinity of fluorotamoxifen, a possible estrogen-receptor imaging agent, J. Med. Chem. 28:1504, 1985.Google Scholar
  14. R. McCague and G. Leclercq. Synthesis, conformational considerations and estrogen receptor binding of 1-[42-dimethylaminoethoxyphenyl]-1,2-diphenylbutane, J. Med. Chem. 30:1761, 1987.Google Scholar
  15. 15.
    B.S. Katzenellenbogen, M.J. Norman, R.L. Eckert, S.W. Peitz and W.F. Mangel. Bioactivities, estrogen receptor interactions and plasminogen activator-inducing activities of tamoxifen and hydroxytamoxifen isomers in MCF-7 human breast cancer cells, Cancer Res. 44, 112, 1984.Google Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • David J. Yang
    • 1
  • Ali M. Emran
    • 3
  • Wayne Tansey
    • 1
  • Kenneth C. Wright
    • 1
  • Li-Ren Kuang
    • 1
  • Gregg Reger
    • 2
  • Roy Tilbury
    • 4
  • Sidney Wallace
    • 1
  • E. Edmund Kim
    • 1
  1. 1.Divisions of Diagnostic ImagingThe University of Texas M.D. Anderson Cancer CenterHoustonUSA
  2. 2.Medical OncologyThe University of Texas M.D. Anderson Cancer CenterHoustonUSA
  3. 3.Positron Diagnostic and Research CenterHoustonUSA
  4. 4.The University of Texas Health Science CenterHoustonUSA

Personalised recommendations