title: Fully automated production of diverse 18F-labeled PET tracers on the ELIXYS multireactor radiosynthesizer without hardware modification.
abstract: Fully automated radiosynthesizers are continuing to be developed to meet the growing need for the reliable production of PET tracers made under current good manufacturing practice guidelines. There is a current trend toward supporting kitlike disposable cassettes that come preconfigured for particular tracers, thus eliminating the need for cleaning protocols between syntheses and enabling quick transitions to synthesizing other tracers. Though ideal for production, these systems are often limited for the development of novel tracers because of pressure, temperature, and chemical compatibility considerations. This study demonstrated the versatile use of the ELIXYS fully automated radiosynthesizer to adapt and produce 8 different (18)F-labeled PET tracers of varying complexity.
  
  
  METHODS
  Three-reactor syntheses of 2-deoxy-2-(18)F-fluoro-β-d-arabinofuranosylcytosine (d-(18)F-FAC), 2-deoxy-2-(18)F-fluoro-5-methyl-β-l-arabinofuranosyluracil (l-(18)F-FMAU), and 2-deoxy-2-(18)F-fluoro-5-ethyl-β-d-arabinofuranosyluracil (d-(18)F-FEAU) along with the 1-reactor syntheses of d-(18)F-FEAU, (18)F-FDG, 3-deoxy-3-(18)F-fluoro-l-thymidine ((18)F-FLT), (18)F-fallypride, 9-(4-(18)F-fluoro-3-hydroxymethylbutyl)-guanine ((18)F-FHBG), and N-succinimidyl-4-(18)F-fluorobenzoate ((18)F-SFB), were all produced using ELIXYS without the need for any hardware modifications or reconfiguration. Synthesis protocols were adapted and slightly modified from those in the literature but were not fully optimized. Furthermore, (18)F-FLT, (18)F-FDG, and (18)F-fallypride were produced sequentially on the same day and used for preclinical imaging of A431 tumor-bearing severe combined immunodeficient mice and wild-type BALB/c mice. To assess future translation to the clinical setting, several batches of tracers were subjected to a full set of quality control tests.
  
  
  RESULTS
  All tracers were produced with radiochemical yields comparable to those in the literature. (18)F-FLT, (18)F-FDG, and (18)F-fallypride were successfully used to image the mice, with results consistent with those reported in the literature. All tracers that were subjected to clinical quality control tests passed.
  
  
  CONCLUSIONS
  The ELIXYS radiosynthesizer facilitates rapid tracer development and is capable of producing multiple (18)F-labeled PET tracers suitable for clinical applications using the same hardware setup.
authors.affiliation: Department of Bioengineering, Henry Samueli School of Engineering, UCLA, Los Angeles, California Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California Crump Institute for Molecular Imaging, David Geffen School of Medicine, UCLA, Los Angeles, California.
authors.forename: Mark
authors.initials: M
authors.lastname: Lazari
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California Crump Institute for Molecular Imaging, David Geffen School of Medicine, UCLA, Los Angeles, California.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Collins
authors.affiliation: Molecular Imaging Program at Stanford (MIPS) Department of Radiology, Stanford University, Stanford, California.
authors.forename: Bin
authors.initials: B
authors.lastname: Shen
authors.affiliation: Sofie Biosciences, Inc., Culver City, California; and.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Farhoud
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California Ahmanson Translational Imaging Division, David Geffen School of Medicine, UCLA, Los Angeles, California.
authors.forename: Daniel
authors.initials: D
authors.lastname: Yeh
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California Crump Institute for Molecular Imaging, David Geffen School of Medicine, UCLA, Los Angeles, California Sofie Biosciences, Inc., Culver City, California; and.
authors.forename: Brandon
authors.initials: B
authors.lastname: Maraglia
authors.affiliation: Molecular Imaging Program at Stanford (MIPS) Department of Radiology, Stanford University, Stanford, California.
authors.forename: Frederick T
authors.initials: FT
authors.lastname: Chin
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California Ahmanson Translational Imaging Division, David Geffen School of Medicine, UCLA, Los Angeles, California.
authors.forename: David A
authors.initials: DA
authors.lastname: Nathanson
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California Crump Institute for Molecular Imaging, David Geffen School of Medicine, UCLA, Los Angeles, California Sofie Biosciences, Inc., Culver City, California; and.
authors.forename: Melissa
authors.initials: M
authors.lastname: Moore
authors.affiliation: Department of Bioengineering, Henry Samueli School of Engineering, UCLA, Los Angeles, California Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California Crump Institute for Molecular Imaging, David Geffen School of Medicine, UCLA, Los Angeles, California mvandam@mednet.ucla.edu.
authors.forename: R Michael
authors.initials: RM
authors.lastname: van Dam
mesh_terms: D000818:Animals; D060326:Chemistry Techniques, Synthetic / Q000295:instrumentation* / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000008:administration & dosage / Q000138:chemical synthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D049268:Positron-Emission Tomography / Q000379:methods*; D011786:Quality Control; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000138:chemical synthesis*; D012984:Software; D051598:Whole Body Imaging / Q000379:methods*
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: 18F-FAC; 18F-FEAU; 18F-FMAU; automated radiosynthesis; radiochemistry kits