title: Optimization of the preparation of fluorine-18-labeled steroid receptor ligands 16alpha-[18F]fluoroestradiol (FES), [18F]fluoro furanyl norprogesterone (FFNP), and 16beta-[18F]fluoro-5alpha-dihydrotestosterone (FDHT) as radiopharmaceuticals.
abstract: Fluorine-18-labeled steroid receptor tracers, 16α-[(18)F]fluoroestradiol (FES), [(18)F]fluoro furanyl norprogesterone (FFNP), and 16β-[(18)F]fluoro-5α-dihydrotestosterone (FDHT), are important imaging tools for studies of breast and prostate cancers using positron emission tomography (PET). The automated production of these ligands with high specific activity (SA) as radiopharmaceuticals requires modification and optimization of the currently reported methods. [(18)F]FES with high SA was synthesized in over 60% radiochemical yield (RCY) at the end of synthesis (EOS) using a small amount of precursor (1) (as low as 0.3 mg) and 1 M H2SO4 for deprotection of the intermediate (2). [(18)F]FFNP was synthesized in up to 77% RCY at EOS using the triflate precursor (4) at room temperature or in 25% RCY using the mesylate precursor (6) at 65°C. Both methods are highly reproducible and afford high SA. [(18)F]FDHT was synthesized by radiofluoride incorporation at room temperature, reduction with NaBH4 , and deprotection with HCl/acetone, giving [(18)F]FDHT in up to 75% yield (RCY). All of these methods can be easily translated to automated production. The information provided here will aid in the development of automated production of these steroid receptor tracers with high or improved yields, optimal SA, and ease of processing for research and clinical use.
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO, 63110, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhou
authors.forename: Mai
authors.initials: M
authors.lastname: Lin
authors.forename: Norio
authors.initials: N
authors.lastname: Yasui
authors.forename: Mohammed H
authors.initials: MH
authors.lastname: Al-Qahtani
authors.forename: Carmen S
authors.initials: CS
authors.lastname: Dence
authors.forename: Sally
authors.initials: S
authors.lastname: Schwarz
authors.forename: John A
authors.initials: JA
authors.lastname: Katzenellenbogen
mesh_terms: D013196:Dihydrotestosterone / Q000737:chemistry*; D015195:Drug Design; D004958:Estradiol / Q000737:chemistry*; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D007553:Isotope Labeling; D009653:Norprogesterones / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis; D011987:Receptors, Steroid / Q000037:antagonists & inhibitors*
chemical_list: D005462:Fluorine Radioisotopes; D009653:Norprogesterones; D019275:Radiopharmaceuticals; D011987:Receptors, Steroid; D013196:Dihydrotestosterone; D004958:Estradiol
keywords: FDHT; FES; FFNP; PET; radiopharmaceuticals; steroid receptor ligand