text: NAVER Academic > Chiral dimethylamine flutamide derivatives—modeling, synthesis, androgen receptor affinities and carbon-11 labeling
  Chiral dimethylamine flutamide derivatives—modeling, synthesis, androgen receptor affinities and carbon-11 labeling
  Jacobson Orit, Laky Desideriu, Carlson Kathryn E, Elgavish Sharona, Gozin Michael, Even-Sapir Einat, Leibovitc Ilan, Gutman Mordechai, Chisin Roland, Katzenellenbogen John A, Mishani Eyal
  Department of Medical Biophysics and Nuclear Medicine, The Hebrew University of Jerusalem, Hadassah Hospital, Jerusalem 91120, Israel, Department of Chemistry, University of Illinois, Urbana, IL 61801, USA, Bioinformatics Unit, The Hebrew University of Jerusalem, Jerusalem 91120, Israel, School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 69978, Israel, Department of Nuclear Medicine, Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv 64239, Israel, Department of Urology, Meir Medical Center, Sackler School of Medicine, Tel Aviv University, Kfar Sava 44281, Israel, Department of Surgery A, Sapir Medical Center, Sackler School of Medicine, Tel Aviv University, Kfar Sava 44281, Israel
  NUCLEAR MEDICINE AND BIOLOGY SCI(E) SCOPUS
  695p ~ 704p ISSN 0969-8051 E-ISSN 1872-9614
  10.1016/j.nucmedbio.2006.05.010
  Natural Sciences > Biology , Medicine > Nuclear Medicine
  Androgen receptor, Prostate cancer, PET, Carbon-11, Carbon Radioisotopes, diagnostic use, Flutamide, analogs & derivatives, metabolism, Humans, Isotope Labeling, Male, Models, Molecular, Positron-Emission Tomography, Prostatic Neoplasms, chemistry, Radiopharmaceuticals, chemical synthesis, Receptors, Androgen, analysis
  Most prostate cancers are androgen dependent upon initial diagnosis. On the other hand, some very aggressive forms of prostate cancer were shown to have lost the expression of the androgen receptor (AR). Although the AR is routinely targeted in endocrine treatment, the clinical outcome remains suboptimal. Therefore, it is crucial to demonstrate the presence and activity of the AR in each case of prostate cancer, before and after treatment. While noninvasive positron emission tomography (PET) has the potential to determine AR expression of tumor cells in vivo, fully optimized PET imaging agents are not yet available. Based on molecular modeling, three novel derivatives of hydroxyflutamide (Compounds 1–3) were designed and synthesized. They contain an electron-rich group (dimethylamine) located on the methyl moiety, which may confer a better stability to the molecule in vivo. Compounds 1–3 have AR binding that is similar or higher than that of the currently used commercial drugs. An automated carbon-11 radiolabeling route was developed, and the compounds were successfully labeled with a 10–15% decay-corrected radiochemical yield, 99% radiochemical purity and a specific activity of 4Ci/μmol end of bombardment ( n=15). These labeled biomarkers may facilitate the future quantitative molecular imaging of AR-positive prostate cancer using PET and may also allow for image-guided treatment of prostate cancer.
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