Nuclear Medicine and Biology
Volume 33, Issue 6 , Pages 705-713 , August 2006

Synthesis and biological evaluation of a nonsteroidal bromine-76-labeled androgen receptor ligand 3-[76Br]bromo-hydroxyflutamide

  • Ephraim E. Parent

      Affiliations

    • Department of Chemistry, University of Illinois, Urbana, IL 61801, USA
  • ,
  • Carl Jenks

      Affiliations

    • Washington University School of Medicine, St. Louis, MO 63110, USA
  • ,
  • Terry Sharp

      Affiliations

    • Washington University School of Medicine, St. Louis, MO 63110, USA
  • ,
  • Michael J. Welch

      Affiliations

    • Washington University School of Medicine, St. Louis, MO 63110, USA
  • ,
  • John A. Katzenellenbogen

      Affiliations

    • Department of Chemistry, University of Illinois, Urbana, IL 61801, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 217 333 6310.

Received 28 April 2006 ,Revised 25 May 2006 ,Accepted 30 May 2006.

References 

  1. Jemal A, Murray T, Samuels A, Ghafoor A, Ward E, Thun MJ. Cancer statistics, 2003. CA: A Cancer J Clin. 2003;53:5–26
  2. Rokhlin OW, Taghiyev AF, Guseva NV, Glover RA, Chumakov PM, Kravchenko JE, et al. Androgen regulates apoptosis induced by TNFR family ligands via multiple signaling pathways in LNCaP. Oncogene. 2005;24:6773–6784
  3. Coffey RNT, Watson RWG, O'Neill AJ, McEleny K, Fitzpatrick JM. Androgen-mediated resistance to apoptosis. Prostate (New York, NY, United States). 2002;53:300–309
  4. Messing EM, Manola J, Sarosdy M, Wilding G, Crawford ED, Trump D. Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. N Engl J Med. 1999;341:1781–1788
  5. Huggins C. Endocrine-induced regression of cancers. Cancer Res. 1967;27:1925–1930
  6. Choe YS, Lidstroem PJ, Chi DY, Bonasera TA, Welch MJ, Katzenellenbogen JA. Synthesis of 11β-[18F]fluoro-5α-dihydrotestosterone and 11β-[18F]fluoro-19-nor-5α-dihydrotestosterone: preparation via halofluorination–reduction, receptor binding, and tissue distribution. J Med Chem. 1995;38:816–825
  7. Liu A, Dence CS, Welch MJ, Katzenellenbogen JA. Fluorine-18-labeled androgens: radiochemical synthesis and tissue distribution studies on six fluorine-substituted androgens, potential imaging agents for prostatic cancer. J Nucl Med. 1992;33:724–734
  8. Liu A, Katzenellenbogen JA, VanBrocklin HF, Mathias CJ, Welch MJ. 20-[18F]Fluoromibolerone, a positron-emitting radiotracer for androgen receptors: synthesis and tissue distribution studies. J Nucl Med. 1991;32:81–88
  9. Dehdashti F, Picus J, Michalski JM, Dence CS, Siegel BA, Katzenellenbogen JA, et al. Positron tomographic assessment of androgen receptors in prostatic carcinoma. Eur J Nucl Med Mol Imaging. 2005;32:344–350
  10. Larson SM, Morris M, Gunther I, Beattie B, Humm JL, Akhurst TA, et al. Tumor localization of 16β-18F-fluoro-5α-dihydrotestosterone versus 18F-FDG in patients with progressive, metastatic prostate cancer. J Nucl Med. 2004;45:366–373
  11. Small EJ, Halabi S, Dawson NA, Stadler WM, Rini BI, Picus J, et al. Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583). J Clin Oncol. 2004;22:1025–1033
  12. Scher HI, Liebertz C, Kelly WK, Mazumdar M, Brett C, Schwartz L, et al. Bicalutamide for advanced prostate cancer: the natural versus treated history of disease. J Clin Oncol. 1997;15:2928–2938
  13. Fowler JE, Pandey P, Seaver LE, Feliz TP. Prostate specific antigen after gonadal androgen withdrawal and deferred flutamide treatment. J Urol. 1995;154:448–453
  14. Scher HI, Kelly WK. Flutamide withdrawal syndrome: its impact on clinical trials in hormone-refractory prostate cancer. J Clin Oncol. 1993;11:1566–1572
  15. Small EJ, Srinivas S. The antiandrogen withdrawal syndrome. Experience in a large cohort of unselected patients with advanced prostate cancer. Cancer. 1995;76:1428–1434
  16. Figg WD, Sartor O, Cooper MR, Thibault A, Bergan RC, Dawson N, et al. Prostate specific antigen decline following the discontinuation of flutamide in patients with stage D2 prostate cancer. Am J Med. 1995;98:412–414
  17. Taplin M-E, Bubley GJ, Shuster TD, Frantz ME, Spooner AE, Ogata GK, et al. Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer. N Engl J Med. 1995;332:1393–1398
  18. Oh WK, Manola J, Bittmann L, Brufsky A, Kaplan ID, Smith MR, et al. Finasteride and flutamide therapy in patients with advanced prostate cancer: response to subsequent castration and long-term follow-up. Urology. 2003;62:99–104
  19. Jacobson O, Bechor Y, Icar A, Novak N, Birman A, Marom H, et al. Prostate cancer PET bioprobes: synthesis of [18F]-radiolabeled hydroxyflutamide derivatives. Bioorg Med Chem. 2005;13:6195–6205
  20. Anonymous . Flutamide for prostate cancer. Med Lett Drugs Ther. 1989;31:72
  21. Katchen B, Buxbaum S. Disposition of a new, nonsteroid, antiandrogen, α,α,α-trifluoro-2-methyl-4′-nitro-m-propionotoluidide (flutamide), in men following a single oral 200 mg dose. J Clin Endocrinol Metab. 1975;41:373–379
  22. Wang H-X, Ma X-C, Deng Q-L, Li D. Cytotoxicity of flutamide and 2-hydroxyflutamide and their effects on CYP1A2 mRNA in primary rat hepatocytes. Acta Pharmacol Sin. 2002;23:562–566
  23. Shet MS, McPhaul M, Fisher CW, Stallings NR, Estabrook RW. Metabolism of the antiandrogenic drug (flutamide) by human CYP1A2. Drug Metab Dispos. 1997;25:1298–1303
  24. Labrie F. Mechanism of action and pure antiandrogenic properties of flutamide. Cancer (New York, NY, United States). 1993;72:3816–3827
  25. Hallowes R, Cox S, Hayward S, Deshpande N, Towler J. Effects of flutamide and hydroxyflutamide on the growth of human benign prostatic hyperplasia cells in primary culture: a preliminary report. Anticancer Res. 1991;11:1799–1805
  26. Dalton JT, Mukherjee A, Zhu Z, Kirkovsky L, Miller DD. Discovery of nonsteroidal androgens. Biochem Biophys Res Commun. 1998;244:1–4
  27. Yin D, He Y, Perera MA, Hong SS, Marhefka C, Stourman N, et al. Key structural features of nonsteroidal ligands for binding and activation of the androgen receptor. Mol Pharmacol. 2003;63:211–223
  28. He Y, Yin D, Perera M, Kirkovsky L, Stourman N, Li W, et al. Novel nonsteroidal ligands with high binding affinity and potent functional activity for the androgen receptor. Eur J Med Chem. 2002;37:619–634
  29. Bohl CE, Miller DD, Chen J, Bell CE, Dalton JT. Structural basis for accommodation of nonsteroidal ligands in the androgen receptor. J Biol Chem. 2005;280:37747–37754
  30. Pangborn AB, Giardello MA, Grubbs RH, Rosen RK, Timmers FJ. Safe and convenient procedure for solvent purification. Organometallics. 1996;15:1518–1520
  31. Still WC, Kahn M, Mitra A. Rapid chromatographic technique for preparative separations with moderate resolution. J Org Chem. 1978;43:2923–2925
  32. Liu A, Carlson KE, Katzenellenbogen JA. Synthesis of high-affinity fluorine-substituted ligands for the androgen receptor. Potential agents for imaging prostatic cancer by positron emission tomography. J Med Chem. 1992;35:2113–2129
  33. Brandes SJ, Katzenellenbogen JA. Fluorinated androgens and progestins: molecular probes for androgen and progesterone receptors with potential use in positron emission tomography. Mol Pharmacol. 1987;32:391–403
  34. McCarthy TJ, McCarthy DW, Laforest R, Bigott HM, Wust F, Reichert DE, et al. Non-standard isotope production and applications at Washington University. AIP Conf Proc. 2001;576:841–844
  35. Tucker H, Crook JW, Chesterson GJ. Nonsteroidal antiandrogens. Synthesis and structure–activity relationships of 3-substituted derivatives of 2-hydroxypropionanilides. J Med Chem. 1988;31:954–959
  36. Sharp TL, Dence CS, Engelbach JA, Herrero P, Gropler RJ, Welch MJ. Techniques necessary for multiple tracer quantitative small-animal imaging studies. Nucl Med Biol. 2005;32:875–884
  37. Garg PK, Labaree DC, Hoyte RM, Hochberg RB. [7α-18F]Fluoro-17α-methyl-5α-dihydrotestosterone: a ligand for androgen receptor-mediated imaging of prostate cancer. Nucl Med Biol. 2001;28:85–90
  38. Jagoda E, Contoreggi C, Lee M-J, Kao C-HK, Szajek LP, Listwak S, et al. Autoradiographic visualization of corticotropin releasing hormone type 1 receptors with a nonpeptide ligand: synthesis of [76Br]MJL-1-109-2. J Med Chem. 2003;46:3559–3562
  39. Coleman RS, Seevers RH, Friedman AM. Aromatic radiobromination without added carrier. J Chem Soc, Chem Commun. 1982;1276–1277
  40. Welch MJ, Redvanly CS and Editors; Handbook of radiopharmaceuticals: radiochemistry and applications, West Sussex: John Wiley & Sons Ltd, 2003.
  41. Nicolaou KC, Sugita K, Baran PS, Zhong YL. Iodine(V) reagents in organic synthesis: Part 2. Access to complex molecular architectures via Dess–Martin periodinane-generated o-imidoquinones. J Am Chem Soc. 2002;124:2221–2232
  42. Suau R, de Inestrosa Villatoro EP. The photochemistry of N-phenyl phthalonimide: formation of substituted dihydroisocoumarins in the presence of tertiary amines. Tetrahedron. 1995;51:6293–6302
  43. Onaka M, Sugita K, Takeuchi H, Izumi Y. Regioselective ring openings of 2,3-epoxy alcohols with ammonium halides and sodium benzenethiolate supported on zeolite CaY. J Chem Soc, Chem Commun. 1988;1173–1174
  44. Pearson WH, Lovering FE. Assembly of 3α-arylperhydroindoles by the intramolecular cycloaddition of 2-azaallyl anions with alkenes. Total syntheses of (±)-crinine, (±)-6-epicrinine, (−)-amabiline, and (−)-augustamine. J Organ Chem. 1998;63:3607–3617
  45. Gao Y, Sharpless KB. Vicinal diol cyclic sulfates. Like epoxides only more reactive. J Am Chem Soc. 1988;110:7538–7539
  46. Koskinen AMP, Karvinen EK, Siirila JP. Enantioselective synthesis of the Taxol and Taxotere side chains. J Chem Soc, Chem Commun. 1994;21–22
  47. Berridge MS, Franceschini MP, Rosenfeld E, Tewson TJ. Cyclic sulfates: useful substrates for selective nucleophilic substitution. J Organ Chem. 1990;55:1211–1217
  48. Romer J, Fuchtner F, Steinbach J, Kasch H. Simultaneous preparation of 16α-[18F]fluoroestradiol-sulfamates in an automated module. A high-yield procedure for 16α-[18F]fluoroestradiol-17β-sulfamate. J Label Comp Radiopharm. 2001;44:689–700
  49. Hoyte RM, Borderon K, Bryson K, Allen R, Hochberg RB, Brown TJ. Synthesis and evaluation of 7α-iodo-5α-dihydrotestosterone as a potential radioligand for androgen receptor. J Med Chem. 1994;37:1224–1230
  50. Carlson KE, Katzenellenbogen JA. A comparative study of the selectivity and efficiency of target tissue uptake of five tritium-labeled androgens in the rat. J Steroid Biochem. 1990;36:549–561

PII: S0969-8051(06)00101-6

doi: 10.1016/j.nucmedbio.2006.05.009

Nuclear Medicine and Biology
Volume 33, Issue 6 , Pages 705-713 , August 2006