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.
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References
J.L. Wittliff. Steroid-hormone receptors in breast cancer, Cancer Res. 53: 630 (1984).
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).
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).
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).
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).
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).
W.C. Still, M. Kahn and A. Mitra. Rapid chromatographic technique for preparative separations with moderate resolution, J. Org. Chem. 43, 2923 (1978).
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).
J.H. Fishman. Stabilization of estradiol-receptor complexes by elimination of cytosolic factors, Biochem. Biophys. Res. Commun. 110:713 (1983).
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).
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).
T. Mosmann, Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assays, J. Immunol. Methods 65:55 (1983).
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.
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.
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.
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© 1991 Springer Science+Business Media New York
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Yang, D.J. et al. (1991). Potential Breast Tumor Imaging Agents: Fluorotamoxifen and Derivatives. In: Emran, A.M. (eds) New Trends in Radiopharmaceutical Synthesis, Quality Assurance, and Regulatory Control. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-0626-7_9
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DOI: https://doi.org/10.1007/978-1-4899-0626-7_9
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