Prostate cancer PET bioprobes: synthesis of [18F]-radiolabeled hydroxyflutamide derivatives.
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.
Jacobson
Orit
O
Department of Medical Biophysics and Nuclear Medicine, The Hebrew University of Jerusalem, Hadassah Hospital, Jerusalem 91120, Israel.
Bechor
Yossi
Y
Icar
Avi
A
Novak
Nurit
N
Birman
Atalia
A
Marom
Hanit
H
Fadeeva
Ludmila
L
Golan
Elizabeth
E
Leibovitch
Ilan
I
Gutman
Mordechai
M
Even-Sapir
Einat
E
Chisin
Roland
R
Gozin
Michael
M
Mishani
Eyal
E
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
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