Advertisement

Radiolabeled Tamoxifen Analogues for Imaging Breast Cancer with Spect

  • David J. Yang
  • Matthew B. Gretzer
  • Li-Ren Kuang
  • Abdallah Cherif
  • Chun Li
  • Miguel F. Diaz
  • Chun-Wei Liu
  • Ali Emran
  • Wayne Tansey
  • Sidney Wallace

Abstract

This study is aimed at developing SPECT ligands to image breast tumors. 99mTc-labeled tamoxifen (TX) analogue was prepared by reacting hydroxyethylthio TX analogue with reduced Tc-IV. The yield was 50–60% (purity >99%). 131I-TX was prepared by treating tosyl-TX with Na131I. The yield was 20–25% (>99% purity). Biodistribution studies of both analogues were performed in DMBA-induced mammary tumor-bearing rats (10 μCi/rat, i.v., n=3/timeinterval). Biodistribution 99mTc-TX at 1, 2, 4, 6 and 18 hrs showed a tumor uptake value (% injected dose/gram tissue) of 0.37±0.058, 0.38±0.066, 0.27±0.041, 0.28±0.124 and 0.10±0.013. Tumor/blood ratio ranged from 0.11 to 0.07. Tumor/muscle ratio ranged from 5.68 to 7.38. Biodistribution of 131I-TX at 1, 3, 6 and 24 hrs showed a tumor uptake value 0.18±0.062, 0.23±0.152, 0.26±0.166 and 0.27±0.016. When rats primed with estradiol (60 μg/rat, 3 days, s.c), the value changed to 0.30±0.033, 0.42± to 0.039, 0.48±0.107, and 0.40±0.123. Tumor/blood ratio ranged from 1.95 to 11.0. When rats pretreated with DES (1.2 mg/rat, iv), the tumor uptake value changed to 0.32±0.058 (99mTc-TX, 2 h) and 0.22±0.059 (131I-TX, 6 h). In rats pretreated with estradiol, a significant increase in tumor uptake value was observed after 131I-TX postinjection. 99mTc-TX uptake in tumor could not be blocked by DES, suggesting the uptake was not due to a receptor-mediated process. 131I-TX may be useful in differentiating functioning ER(+) breast tumors.

Keywords

Estrogen Receptor Tumor Uptake Biodistribution Study Gamma Scintigraphy Estrogen Receptor Assay 
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.
    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. 20:41–46 (1984).PubMedCrossRefGoogle Scholar
  2. 2.
    A.H. McGuire, F. Dehdashti, B.A. Siegel, A.P. Lyss, J.W. Brodack, C.J. Mathias, M.A. Mintum, J.A. Katzenellenbogan and M.J. Welch. Postiron tomographic assessment of 16-alpha-[18F]fluoro-17-beta-estradiol uptake in metastatic breast carcinoma. J. Nucl. Med. 32:1526–1531 (1991).PubMedGoogle Scholar
  3. 3.
    M.E. McManaway, E.M. Jagoda, A. Kasid, W.C. Eckelman, B.E. Francis, S.M. Larson, R.E. Gibson, R.C. Reba and M.E. Lippman. [125I]17-beta-iodovinyl-11-beta-methoxyestradiol: in vivo and in vitro properties of a high affinity estrogen-receptor radiopharmaceutical. J. Nucl. Med. 25:472–477 (1984).Google Scholar
  4. 4.
    E.M. Jagoda, R.E. Gibson, H. Goodgold, N. Ferreira, B.E. Francis, R.C. Reba, W.J. Rzeszotarski and W.C. Eckelman. [125I]17-Iodovinyl-ll-beta-methoxyestradiol: in vivo and in vitro properties of a high affinity estrogen-receptor radiopharmaceutical. J. Nucl. Med. 25:472–477 (1984).PubMedGoogle Scholar
  5. 5.
    J.T. Hamm and J.C. Allegra. Hormonal therapy for cancer. In: Witts RE, ed. Manual of Oncologic Therapeutics. New York: Lippincott; 122–126 (1991).Google Scholar
  6. 6.
    J.L. Wittliff. Steroid-hormone receptor in breast cancer. Cancer Res. 53:630–643 (1984).Google Scholar
  7. 7.
    D. Yang, A. Cherif, W. Tansey, L-R Kuang, K. Wright, C. Li, E.E. Kim and S. Wallace. N1N-diethylfluoromethyltamoxifen: synthesis assignment of 1H and 13C spectra and receptor assay. Eur. J. Medicinal Chem. 27:919–924 (1992).CrossRefGoogle Scholar
  8. 8.
    D. Yang and S. Wallace. High affinity tamoxifen derivatives and uses thereof. United States Patent Number 5,192,525, March 9, 1993.Google Scholar
  9. 9.
    D. Yang, S. Wallace, K.C. Wright, J.E. Price, L-R Kuang and E.E. Kim. Imaging of estrogen receptors with PET using 18F-fluoro analogue of tamoxifen. Radiology 185–186 (1992).Google Scholar
  10. 10.
    D.J. Yang, L-R Kuang, A. Cherif, W. Tansey, C. Li, W.J. Lin, C-W Liu, E.E. Kim and S. Wallace. Synthesis of 18F-alanine and 18F-tamoxifen for breast tumor imaging. J. Drug Targeting (1992) in press.Google Scholar
  11. 11.
    D.J. Yang, W.H. Wong, W. Tansey, K. Vargas, R. Tilbury, W. Broussard, L-R Kuang, S. Wallace and E.E. Kim. [18F]Fluoro analog of tamoxifen:radiosynthesis and imaging of estrogen receptors with PET. L Nucl. Med. 33(5), 985 (1992).Google Scholar
  12. 12.
    J.D. Liverant and W. Wolf. Studies on the reduction of [99mTc]TcO4- by hydrochloric acid. Int. J. Appl. Radiat. Isot. (33)857–860 (1982).CrossRefGoogle Scholar
  13. 13.
    O.H. Lowry, N.J. Rosebrough, A.L. Farr and R.J. Randall. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193:265–275 (1951).PubMedGoogle Scholar
  14. 14.
    D. Yang, T. Tewson, W. Tansey, L-R Kuang, G. Reger, A. Cherif, K. Wright, R. Moult, R. Tilbury, E.E. Kim, S. Wallace. Halogenated analogs of tamoxifen:synthesis, receptor assay and inhibition of MCF7 cells. J. Pharm. Sciences, (81)622–625 (1992).CrossRefGoogle Scholar
  15. 15.
    V.R. Bezwoda, J.D. Esser, R. Dansey, I. Kessel, M. Lange. The value of estrogen and progesterone receptor determinations in advanced breast cancer. Cancer 68:867–872 (1991).PubMedCrossRefGoogle Scholar
  16. 16.
    B.J. Fernandes, X.Y. Yao, D.J. Sutherland, S. Sidlofsky, M.E. Blackstein. DNA content and estrogen receptors in primary carcinoma of the breast. C.J.S. 34:349–355 (1991).Google Scholar
  17. 17.
    J. Shani, A. Gazit, T. Livshitz, S. Brian. Synthesis and receptor binding of fluorotamoxifen, a possible receptor imaging agent. J. Med. Chem. 28:1504–1511 (1985).PubMedCrossRefGoogle Scholar
  18. 18.
    R.N. Hanson, D.E. Seitz. Tissue distribution of the radiolabeled antiestrogen [125I]iodotamoxifen. Int. J. Nucl. Med. Biol. 9:105–107 (1982).PubMedCrossRefGoogle Scholar
  19. 19.
    S. Ram and L.D. Spicer. J. Labelled Compd. Radiopharm. 27:661–668 (1989).CrossRefGoogle Scholar
  20. 20.
    L. Kangas, A-L Nieminen, G. Blanco, et al. A new triphenylethylene, FC-1157a, antitumor effects. Cancer Chemother. Pharmacol. 17:109–113 (1986).PubMedCrossRefGoogle Scholar
  21. 21.
    S. Kallio, L. Kangas, G. Blanco, R. Johansson, A. Karjalainen, M. Perila, I. Pippo, H. Sunquist, M. Sodervall and R. Toivola. A new triphenylethylene, FC-1157a, hormonal effects. Cancer Chemother. Pharmacol. 17:103–108 (1986).PubMedCrossRefGoogle Scholar
  22. 22.
    K.D. McElvany, J.A. Katzenellenbogen, K.S. Shafter, B.A. Siegel, S.G. Senderoff, M.J. Welch. 16[77Br]Bromoestradiol:dosimetry and preliminary clinical studies. J. Nucl. Med. 23:425–430 (1982).PubMedGoogle Scholar
  23. 23.
    T-L Tsai, B.S. Katzenellenbogen. Antagonism of development and growth of 7, 12-dimethylbenz(a)anthracene-induced rat mammary tumors by the antiestrogen U23, 469 and effects on estrogen and progesterone receptors. Cancer Res. 37:1537–1543 (1977).PubMedGoogle Scholar
  24. 24.
    M.R. Schneider, E.V. Angerer, H. Schonenberger, R.T. Michel, H.P. Fortmeyer. 1,1,2-Triphenylbut-l-enes:relationship between structure, estradiol receptor affinity, and mammary tumor inhibiting properties. J. Med. Chem.25:1070–1077 (1982).PubMedCrossRefGoogle Scholar
  25. 25.
    I.F. Pollack, M.S. Randall, M.P. Kristofik, R.H. Kelly, R.G. Selker and F.T. Vertosick. Effect of tamoxifen on DNA synthesis and proliferation of human malignant glioma lines in vitro. Cancer Res. 50:7134–7138 (1990).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • David J. Yang
    • 1
  • Matthew B. Gretzer
    • 1
  • Li-Ren Kuang
    • 1
  • Abdallah Cherif
    • 1
  • Chun Li
    • 1
  • Miguel F. Diaz
    • 1
  • Chun-Wei Liu
    • 1
  • Ali Emran
    • 2
  • Wayne Tansey
    • 1
  • Sidney Wallace
  1. 1.Division of Diagnostic ImagingThe University of Texas M.D. Anderson Cancer CenterHoustonUSA
  2. 2.Positron Diagnostic and Research CenterThe University of Texas Health Science CenterHoustonUSA

Personalised recommendations