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

Purpose

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.

Procedures

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.

Results

The labeling precursor 3 was obtained in 45 % overall yield. Nucleophilic substitution with K¹⁸F/K_2.2.2 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.

Conclusions

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 %.