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.
Conflict of Interest
The authors declare that they have no conflict of interest.
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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
- F-18 labeling
- Automated radiosynthesis