Nuclear Medicine and Biology
Volume 35, Issue 5 , Pages 615-622 , July 2008

Syntheses and biological activities of novel 2-methoxyestradiol analogs, 2-fluoroethoxyestradiol and 2-fluoropropanoxyestradiol, and a radiosynthesis of 2-[18F]fluoroethoxyestradiol for positron emission tomography

  • Jiyoung Mun

      Affiliations

    • Department of Radiology, Emory University, Atlanta, GA 30322, USA
    • ,
  • Yuefang Wang

      Affiliations

    • Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA
    • ,
  • Ronald J. Voll

      Affiliations

    • Department of Radiology, Emory University, Atlanta, GA 30322, USA
    • ,
  • Daniel Escuin-Borras

      Affiliations

    • Department of Hematology/Oncology, Weill Cornell Medical College of Cornell University, New York, NY 10021,USA
    • ,
  • Paraskevi Giannakakou

      Affiliations

    • Department of Hematology/Oncology, Weill Cornell Medical College of Cornell University, New York, NY 10021,USA
    • ,
  • Mark M. Goodman

      Affiliations

    • Department of Radiology, Emory University, Atlanta, GA 30322, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 404 727 9366; fax: +1 404 727 3488.

Received 4 March 2008 ,Revised 31 March 2008 ,Accepted 1 April 2008.

References 

  1. Ricker JL, Chen Z, Yang XP, Pribluda VS, Swartz GM, Van Waes C. 2-Methoxyestradiol inhibits hypoxia-inducible factor 1a, tumor growth, and angiogenesis and augments paclitaxel efficacy in head and neck squamous cell carcinoma. Clin Cancer Res. 2004;10:8665–8673
  2. Kang SH, Cho HT, Devi S, Zhang Z, Escuin D, Liang Z, et al. Antitumor effect of 2-methoxyestradiol in a rat orthotopic brain tumor model. Cancer Res. 2006;66:11991–11997
  3. Ray G, Dhar G, Van Veldhuizen PJ, Banerjee S, Saxena NK, Sengupta K, et al. Modulation of cell-cycle regulatory signaling network by 2-methoxyestradiol in prostate cancer cells is mediated through multiple signal transduction pathways. Biochemistry. 2006;45:3703–3713
  4. Kimbro KS, Simons JW. Hypoxia-inducible factor-1 in human breast and prostate cancer. Endocr Relat Cancer. 2006;13:739–749
  5. D'Amato RJ, Lin CM, Flynn E, Folkman J, Hamel E. 2-Methoxyestradiol, and endogenous mammalian metabolite, inhibits tubulin polymerization by interacting at the colchicine site. Proc Natl Acad Sci U S A. 1994;91:3964–3968
  6. Mabjeesh NJ, Escuin D, LaVallee TM, Pribluda VS, Swartz GM, Johnson MS, et al. 2ME2 inhibits tumor growth and angiogenesis by disrupting microtubules and dysregulating HIF. Cancer Cell. 2003;3:363–375
  7. James J, Murry DJ, Treston AM, Storniolo AM, Sledge GW, Sidor CM, et al. Phase I safety, pharmacokinetic and pharmacodynamic studies of 2-methoxyestradiol alone or in combination with docetaxel in patients with locally recurrent or metastatic breast cancer. Invest New Drugs. 2007;25:41–48
  8. Mooberry SL. Mechanism of action of 2-methoxyestradiol: new developments. Drug Resist Updat. 2003;6:355–361
  9. Hamel E, Lin CM, Flynn E, D'Amato RJ. Interactions of 2-methoxyestradiol, an endogenous mammalian metabolite, with unpolymerized tubulin and with tubulin polymers. Biochemistry. 1996;35:1304–1310
  10. Mun J, Voll RJ, Goodman MM. Synthesis of 2-[11C]methoxy-3,17β-estradiol to measure the pharmacokinetics of an antitumor drug candidate, 2-methoxy-3,17β-estradiol. J Labelled Comp Radioparm. 2006;49:1117–1124
  11. Cushman M, He HM, Katzenellenbogen JA, Lin CM, Hamel E. Synthesis, antitubulin and antimitotic activity, and cytotoxicity of analogs of 2-methoxyestradiol, an endogenous mammalian metabolite of estradiol that Inhibits tubulin polymerization by binding the colchicine binding site. J Med Chem. 1995;38:2041–2049
  12. Cushman M, He HM, Katzenellenbogen JA, Varma RK, Hamel E, Lin CM, et al. Synthesis of analogs of 2-methoxyestradiol with enhanced inhibitory effects on tubulin polymerization and cancer cell growth. J Med Chem. 1997;40:2323–2334
  13. Cushman M, Mohanakrishnan AK, Hollingshead M, Hamel E. The effect of exchanging various substituents at the 2-position of 2-methoxyestradiol on cytotoxicity in human cancer cell cultures and inhibition of tubulin polymerization. J Med Chem. 2002;45:4748–4754
  14. Nicolaou KC, Namoto KR, Andreas UT, Shoji M, Li J, D'Amico G, et al. Chemical synthesis and biological evaluation of cis- and trans-12,13-cyclopropyl and 12,13-cyclobutyl epothilones and related pyridine side chain analogues. J Am Chem Soc. 2001;123:9313–9323
  15. Skehan P, Storeng R, Scudiero D, Monks A, McMahon J, Vistica D, et al. New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Cancer Inst. 1990;82:1107–1112
  16. Escuin D, Wang Y, Lavallee T, Nettles JH, Snyder JP, Giannakakou P. Development and molecular characterization of a human ovarian cancer cell line resistant to 2-Methoxyestradiol (1A9-2ME2R) [abstract]. In: Proceedings of the 96th Annual Meeting of the American Association for Cancer Research; 2005 Apr 16–20; Anaheim, California (CA). 2005;p. 1202;Abstract nr 5092
  17. Voll RJ, McConathy J, Waldrep MS, Crowe RJ, Goodman MM. Semi-automated preparation of the dopamine transporter ligand [18F]FECNT for human PET imaging studies. Appl Radiat Isot. 2005;63:353–361
  18. Wilson AA, Houle S. Radiosynthesis of carbon-11 labeled N-methyl- 2-(arylthio)benzylamines: potential radiotracers for the serotonin reuptake receptor. J Labelled Comp Radiopharm. 1999;42:1277–1288
  19. He HM, Cushman M. A versatile synthesis of 2-methoxyestradiol, an endogenous metabolite of estradiol which inhibits tubulin polymerization by binding to the colchicine binding site. Bioorg Med Chem Lett. 1994;4:1725–1728
  20. Wang Z, Cushman M. An optimized synthesis of 2-methoxyestradiol, a naturally occurring human metabolite with anticancer activity. Syn Commun. 1998;28:4431–4437

PII: S0969-8051(08)00079-6

doi: 10.1016/j.nucmedbio.2008.04.003

Nuclear Medicine and Biology
Volume 35, Issue 5 , Pages 615-622 , July 2008

Article Tools

* Image Usage & Resolution