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

Orit Jacobson, Desideriu Laky, Kathryn E. Carlson, Sharona Elgavish, Michael Gozin, Einat Even-Sapir, Ilan Leibovitc, Mordechai Gutman, Roland Chisin, John A. Katzenellenbogen, Eyal Mishani*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


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.

Original languageAmerican English
Pages (from-to)695-704
Number of pages10
JournalNuclear Medicine and Biology
Issue number6
StatePublished - Aug 2006


  • Androgen receptor
  • Carbon-11
  • PET
  • Prostate cancer


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