Fully Automated Radiosynthesis of 2-[18F]Fludarabine for PET Imaging of Low-Grade Lymphoma



An efficient and fully automated radiosynthesis of 2-[18F]fluoro-9-β-d-arabinofuranosyl-adenine (2-[18F]fludarabine, [18F]-5) based on a GE TRACERlab™ FX-FN module has been developed.


A 2-nitro purine derivative 3 was developed as precursor for labeling with fluorine-18. The radiosynthesis of [18F]-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, [18F]-5 was purified by semi-preparative high-pressure liquid chromatography (HPLC) and a quality control was established.


The labeling precursor 3 was obtained in 45 % overall yield. Nucleophilic substitution with K18F/K2.2.2 afforded protected 2-[18F]fludarabine ([18F]-4) in 73 ± 4 % , radiochemical yield (decay corrected to the end of bombardment (EOB)) and based on the initial [18F]F activity. An aqueous ammonia/methanol solution was used for the deprotection reaction and gave the desired [18F]-5 in 67 ± 3 % yield after 20 min at 70 °C based on HPLC profile.


The process afforded pure 2-[18F]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 %.

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This work has been in part supported by a grant from the French National Agency for Research called “Investissements d’Avenir” no. ANR-11-LABEX-0018-01, the Commissariat à l’énergie atomique et aux énergies alternatives (CEA) and the Région Basse Normandie. The authors wish to thank Dr. Eric T. MacKenzie for his helpful comments and discussion.

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The authors declare that they have no conflict of interest.

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Correspondence to Louisa Barré.

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Guillouet, S., Patin, D., Tirel, O. et al. Fully Automated Radiosynthesis of 2-[18F]Fludarabine for PET Imaging of Low-Grade Lymphoma. Mol Imaging Biol 16, 28–35 (2014). https://doi.org/10.1007/s11307-013-0657-4

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Key words

  • F-18 labeling
  • 2-[18F]Fludarabine
  • Automated radiosynthesis
  • PET
  • Nucleoside
  • Lymphoma