title: Fully-automated synthesis of 16β-(18)F-fluoro-5α-dihydrotestosterone (FDHT) on the ELIXYS radiosynthesizer.
abstract: Noninvasive in vivo imaging of androgen receptor (AR) levels with positron emission tomography (PET) is becoming the primary tool in prostate cancer detection and staging. Of the potential (18)F-labeled PET tracers, (18)F-FDHT has clinically shown to be of highest diagnostic value. We demonstrate the first automated synthesis of (18)F-FDHT by adapting the conventional manual synthesis onto the fully-automated ELIXYS radiosynthesizer. Clinically-relevant amounts of (18)F-FDHT were synthesized on ELIXYS in 90 min with decay-corrected radiochemical yield of 29±5% (n=7). The specific activity was 4.6 Ci/µmol (170 GBq/µmol) at end of formulation with a starting activity of 1.0 Ci (37 GBq). The formulated (18)F-FDHT yielded sufficient activity for multiple patient doses and passed all quality control tests required for routine clinical use.
authors.affiliation: Department of Bioengineering, Henry Samueli School of Engineering, UCLA, Los Angeles, CA, USA; Crump Institute for Molecular Imaging, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Lazari
authors.affiliation: Radiochemistry & Molecular Imaging Probe Core, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Serge K
authors.initials: SK
authors.lastname: Lyashchenko
authors.affiliation: Radiochemistry & Molecular Imaging Probe Core, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Eva M
authors.initials: EM
authors.lastname: Burnazi
authors.affiliation: Radiochemistry & Molecular Imaging Probe Core, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Radiochemistry and Imaging Sciences Service, Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Lewis
authors.affiliation: Department of Bioengineering, Henry Samueli School of Engineering, UCLA, Los Angeles, CA, USA; Crump Institute for Molecular Imaging, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
authors.forename: R Michael
authors.initials: RM
authors.lastname: van Dam
authors.affiliation: Crump Institute for Molecular Imaging, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA. Electronic address: jmmurphy@mednet.ucla.edu.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Murphy
mesh_terms: D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification; D015195:Drug Design; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005462:Fluorine Radioisotopes / Q000737:chemistry* / Q000302:isolation & purification; D007553:Isotope Labeling / Q000295:instrumentation*; D011876:Radionuclide Generators / Q000295:instrumentation*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000302:isolation & purification; D012212:Rheology / Q000295:instrumentation; D012371:Robotics / Q000295:instrumentation*; D013048:Specimen Handling / Q000295:instrumentation
chemical_list: C494901:16-fluorodihydrotestosterone; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D013196:Dihydrotestosterone
keywords: FDHT; Fluorine-18; Fully-automated; LiAlH(4) reduction; PET; Prostate cancer