title: Prostate cancer PET bioprobes: synthesis of [18F]-radiolabeled hydroxyflutamide derivatives.
abstract: Approximately 80-90% of prostate cancers are androgen dependent at initial diagnosis. The androgen receptor (AR) is present in most advanced prostate cancer specimens and is believed to have a critical role in its development. Today, treatment of prostate cancer is done by inhibition of AR using antiandrogens such as flutamide (pro-drug of hydroxyflutamide), nilutamide, and bicalutamide. However, there is currently no noninvasive imaging modalities to detect, guide, and monitor specific treatment of AR-positive prostate cancer. (R)-3-Bromo-N-(4-fluoro-3-(trifluoromethyl)phenyl)-2-hydroxy-2-methyl-propanamide [18F]-1 and N-(4-fluoro-3-(trifluoromethyl)phenyl)-2-hydroxy-2-methylpropanamide [18F]-2, derivatives of hydroxyflutamide, were synthesized as a fluorine-containing imaging agent candidates. A three-step fluorine-18 radiosynthesis route was developed, and the compounds were successfully labeled with a 10+/-3% decay corrected radiochemical yield, 95% radiochemical purity, and a specific activity of 1500+/-200 Ci/mmol end of bombardment (n = 10). These labeled biprobes not only may enable for the future quantitative molecular imaging of AR-positive prostate cancer using positron emission tomography but may also allow for image-guided treatment of prostate cancer.
authors.affiliation: Department of Medical Biophysics and Nuclear Medicine, The Hebrew University of Jerusalem, Hadassah Hospital, Jerusalem 91120, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Jacobson
authors.forename: Yossi
authors.initials: Y
authors.lastname: Bechor
authors.forename: Avi
authors.initials: A
authors.lastname: Icar
authors.forename: Nurit
authors.initials: N
authors.lastname: Novak
authors.forename: Atalia
authors.initials: A
authors.lastname: Birman
authors.forename: Hanit
authors.initials: H
authors.lastname: Marom
authors.forename: Ludmila
authors.initials: L
authors.lastname: Fadeeva
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Golan
authors.forename: Ilan
authors.initials: I
authors.lastname: Leibovitch
authors.forename: Mordechai
authors.initials: M
authors.lastname: Gutman
authors.forename: Einat
authors.initials: E
authors.lastname: Even-Sapir
authors.forename: Roland
authors.initials: R
authors.lastname: Chisin
authors.forename: Michael
authors.initials: M
authors.lastname: Gozin
authors.forename: Eyal
authors.initials: E
authors.lastname: Mishani
mesh_terms: D000726:Androgen Antagonists / Q000138:chemical synthesis* / Q000737:chemistry; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D005485:Flutamide / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging; D011877:Radionuclide Imaging
chemical_list: C507093:(R)-3-bromo-N-(4-fluoro-3-(trifluoromethyl)phenyl)-2-hydroxy-2-methyl-propanamide(18F); D000726:Androgen Antagonists; D005462:Fluorine Radioisotopes; C507092:N-(4-fluoro-3-(trifluoromethyl)phenyl)-2-hydroxy-2-methyl-propanamide(18F); C014290:hydroxyflutamide; D005485:Flutamide