title: Fully automated radiosynthesis of 2-[18F]fludarabine for PET imaging of low-grade lymphoma.
abstract: OBJECTIVE
  An efficient and fully automated radiosynthesis of 2-[(18)F]fluoro-9-β-D-arabinofuranosyl-adenine (2-[(18)F]fludarabine, [(18)F]-5) based on a GE TRACERlab™ FX-FN module has been developed.
  
  
  METHODS
  A 2-nitro purine derivative 3 was developed as precursor for labeling with fluorine-18. The radiosynthesis of [(18)F]-5 was performed in two steps in a single reactor with an intermediary purification on Sep-Pak® silica which involved the addition of a three-way valve on the original module. After hydrolysis, [(18)F]-5 was purified by semi-preparative high-pressure liquid chromatography (HPLC) and a quality control was established.
  
  
  RESULTS
  The labeling precursor 3 was obtained in 45% overall yield. Nucleophilic substitution with K(18)F/K2.2.2 afforded protected 2-[(18)F]fludarabine ([(18)F]-4) in 73 ± 4%, radiochemical yield (decay corrected to the end of bombardment (EOB)) and based on the initial [(18)F]F(-) activity. An aqueous ammonia/methanol solution was used for the deprotection reaction and gave the desired [(18)F]-5 in 67 ± 3% yield after 20 min at 70 °C based on HPLC profile.
  
  
  CONCLUSIONS
  The process afforded pure 2-[(18)F]fludarabine in 48 ± 3% yield (decay corrected to the EOB) in 85 min, with a specific activity of 310 ± 72 GBq/μmol at the end of synthesis (EOS) and a radiochemical purity up to 99%.
authors.affiliation: CEA, I2BM, LDM-TEP, UMR 6301 ISTCT, GIP Cyceron, 14074, Caen, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Guillouet
authors.forename: Delphine
authors.initials: D
authors.lastname: Patin
authors.forename: Olivier
authors.initials: O
authors.lastname: Tirel
authors.forename: Jérôme
authors.initials: J
authors.lastname: Delamare
authors.forename: Fabienne
authors.initials: F
authors.lastname: Gourand
authors.forename: Jean Bernard
authors.initials: JB
authors.lastname: Deloye
authors.forename: Michel
authors.initials: M
authors.lastname: Leporrier
authors.forename: Louisa
authors.initials: L
authors.lastname: Barré
mesh_terms: D001331:Automation; D002851:Chromatography, High Pressure Liquid; D005462:Fluorine Radioisotopes; D006801:Humans; D008223:Lymphoma / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography; D011786:Quality Control; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000138:chemical synthesis
chemical_list: D005462:Fluorine Radioisotopes; D014740:Vidarabine; C024352:fludarabine