Nuclear Medicine and Biology
Volume 33, Issue 6 , Pages 695-704 , August 2006

Chiral dimethylamine flutamide derivatives—modeling, synthesis, androgen receptor affinities and carbon-11 labeling

  • Orit Jacobson

      Affiliations

    • Department of Medical Biophysics and Nuclear Medicine, The Hebrew University of Jerusalem, Hadassah Hospital, Jerusalem 91120, Israel
    • ,
  • Desideriu Laky

      Affiliations

    • Department of Medical Biophysics and Nuclear Medicine, The Hebrew University of Jerusalem, Hadassah Hospital, Jerusalem 91120, Israel
    • ,
  • Kathryn E. Carlson

      Affiliations

    • Department of Chemistry, University of Illinois, Urbana, IL 61801, USA
    • ,
  • Sharona Elgavish

      Affiliations

    • Bioinformatics Unit, The Hebrew University of Jerusalem, Jerusalem 91120, Israel
    • ,
  • Michael Gozin

      Affiliations

    • School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 69978, Israel
    • ,
  • Einat Even-Sapir

      Affiliations

    • Department of Nuclear Medicine, Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv 64239, Israel
    • ,
  • Ilan Leibovitc

      Affiliations

    • Department of Urology, Meir Medical Center, Sackler School of Medicine, Tel Aviv University, Kfar Sava 44281, Israel
    • ,
  • Mordechai Gutman

      Affiliations

    • Department of Surgery A, Sapir Medical Center, Sackler School of Medicine, Tel Aviv University, Kfar Sava 44281, Israel
    • ,
  • Roland Chisin

      Affiliations

    • Department of Medical Biophysics and Nuclear Medicine, The Hebrew University of Jerusalem, Hadassah Hospital, Jerusalem 91120, Israel
    • ,
  • John A. Katzenellenbogen

      Affiliations

    • Department of Chemistry, University of Illinois, Urbana, IL 61801, USA
    • ,
  • Eyal Mishani

      Affiliations

    • Department of Medical Biophysics and Nuclear Medicine, The Hebrew University of Jerusalem, Hadassah Hospital, Jerusalem 91120, Israel
    • Corresponding Author InformationCorresponding author. Tel.: +972 2 677931; fax: +972 2 6421203.

Received 16 April 2006 ,Revised 28 May 2006 ,Accepted 28 May 2006.

References 

  1. Labrie F. Current status of endocrine therapy in localized prostate cancer: cure has become a strong possibility. J Urol. 2004;30(1):3–11
  2. Jemal A, Murray T, Samuels A, Ghafoor A, Ward E, Thun MJ. Cancer statistics 2003. CA Cancer J Clin. 2003;53:5–26
  3. He Y, Yin D-G, Perera MA, 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
  4. Dalton JT, Mukherjee A, Zhu Z, Kirkovsky L, Miller DD. Discovery of nonsteroidal androgens. Biochem Biophys Res Commun. 1998;244:1–4
  5. Heinlein CA, Chang C. Androgen receptor in prostate cancer. Endocr Rev. 2004;25:276–308
  6. Santos AF, Huang H, Tindall D. The androgen receptor: a potential target for therapy of prostate cancer. Steroids. 2004;69(2):79–85
  7. Berrevoets Cor A, Umar A, Brinkmann AO. Antiandrogens: selective androgen receptor modulators. Mol Cell Endocrin. 2002;198:97–103
  8. Wakabayashi KI, Miyachi H, Hashimoto Y, Tanatani A. Novel non-steroidal/non-anilide type androgen antagonist: discovery of 4-substituted pyrrole-2-carboxamides as a new scaffold for androgen receptor ligands. Bioorg Med Chem. 2005;13:2837–2846
  9. De Jong IJ, Pruim J, Elsinga PH, Jongen MM, Mensink HJA, Vaalburg W. Visualisation of bladder cancer using [sup C] C-choline PET: first clinical experience. Eur J Nucl Med. 2002;29:1283–1288
  10. Britton KE, Feneley MR, Jan H, Chengazi VU, Granowska M. Prostate cancer: the contribution of nuclear medicine. BJU Int. 2000;86:135–142
  11. Hofer C, Kubler H, Hartung R, Breul J, Avril N. Diagnosis and monitoring of urological tumors using positron emission tomography. Eur Urol. 2001;40:481–487
  12. De Jong IJ, Pruim J, Elsinga PH, Vaalburg W, Mensink HJA. Visualization of prostate cancer with 11C-choline positron emission tomography. Eur Urol. 2002;42:18–23
  13. Karam JA, Mason RP, Koeneman KS, Antich PP, Benaim EA, Hsieh JT. Molecular imaging in prostate cancer. J Cell Biochem. 2003;90:473–483
  14. Picchio M, Landoni C, Messa C, Gianolli L, Matarrese M, DeCobelli F, et al. Positive [11C]choline and negative [18F]FDG with positron emission tomography in recurrence of prostate cancer. AJR Am J Roentgenol. 2002;179:482–484
  15. 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
  16. Zanzonico PB, Finn R, Pentlow KS, Erdi Y, Beattie B, Akhurst T, et al. PET-based radiation dosimetry in man of 18F-fluorodihydrotestosterone, a new radiotracer for imaging prostate cancer. J Nucl Med. 2004;45:1966–1971
  17. Dehdashti F, Joel P, Michalski JM, Dence CS, Siegel BA, Katzenellenbogen JA, et al. Positron tomographic assessment of androgen receptors in prostatic carcinoma. Eur J Nucl Med Mol Imag. 2005;32:344–350
  18. 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(22):6195–6205
  19. Tucker H, Chesterson GJ. Resolution of the non steroidal antiandrogen 4-cyano-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methyl-3 (trifluoromethyl)propionanilide and the determination of the absolute configuration of the active enantiomer. J Med Chem. 1988;31:885–888
  20. Kirkovsky L, Mukherjee A, Yin DH, Dalton JT, Miller DD. Chiral nonsteroidal affinity ligands for the androgen receptor. Bicalutamide analogues bearing electrophilic groups in the B aromatic ring. J Med Chem. 2000;43:581–590
  21. Marhefka CA, Moore BM, Bishop TC, Kirkovsky L, Mukherjee A, Dalton JT, et al. Homology modeling using multiple molecular dynamics simulations and docking studies of the human androgen receptor ligand binding domain bound to testosterone and nonsteroidal ligands. J Med Chem. 2001;44:1729–1740
  22. Brandes SJ, Katzenellenbogen JA. Fluorinated androgens and progestin: molecular probes for androgen and progesterone receptors with potential use in positron emission tomography. Mol Pharmacol. 1987;32:391–403
  23. Katzenellenbogen JA, Johnson HJ, Myers HN. Photoaffinity labels for estrogen binding proteins of rat uterus. Biochemistry. 1973;12:4085–4092
  24. Carlson KE, Choi I, Gee A, Katzenellenbogen JA. Altered ligand binding properties and enhanced stability of a constitutively active estrogen receptor: evidence that an open pocket conformation is required for ligand interaction. Biochemistry. 1997;36:14897–14905
  25. Crouzel C, Langstrom B, Pike VW, Coenen HH. Recommendation for a practical production of [C-11]MeI. Int J Appl Radiat Isot. 1987;38:601–604
  26. Mishani E, Abourbeha G, Rozen Y, Jacobson O, Laky D, BenDavid I, et al. Novel carbon-11 labeled 4-dimethylamino-but-2-enoic acid [4-(phenylamino)-quinazoline-6-yl]-amides: potential PET bioprobes for molecular imaging of EGFR-positive tumors. Nucl Med Biol. 2004;31:469–476
  27. 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
  28. Glen AT, Hughes LR, Morris JJ, Taylor PJ. In: Structure activity relationships among nonsteroidal antiandrogens. London: Royal Society of Chemistry; 1986;p. 345–361
  29. Parent E, Jenks C, Sharp T, Katenellenbogen J, Welch M. Synthesis and in-vivo characterization of 76Br labeled flutamide and bicalutamide analogs. J Label Compd Radiopharm. 2005;48:S155

PII: S0969-8051(06)00100-4

doi: 10.1016/j.nucmedbio.2006.05.010

Nuclear Medicine and Biology
Volume 33, Issue 6 , Pages 695-704 , August 2006

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