Radiosynthesis of 6‐([18F]fluoroacetamido)‐1‐hexanoicanilide ([18F]FAHA) for PET imaging of histone deacetylase (HDAC)

Radiosynthesis of a novel substrate for histone deacetylase (HDAC), 6‐([18F]fluoroacetamido)‐1‐hexanoicanilide ([18F]FAHA, [18F]‐3) is reported. For precursor synthesis, compound 1 (6‐amino‐1‐hexanoicanilide) was prepared by the reaction of 6‐amino hexanoic acid with thionyl chloride in dichloroethane followed by addition of aniline. Compound 1 was reacted with bromoacetic anhydride in tetrahydrofuran (THF) in the presence of triethylamine to produce the precursor compound 6‐(bromoacetamido)‐1‐hexanoicanilide 2. Fluorination reactions were performed using tetrabutylammonium fluoride in various solvents at 80°C to prepare the unlabeled reference compound 3. Radiofluorinations were performed using either n‐Bu4N18F or K18F/kryptofix, and the crude product was purified by high performance liquid chromatography (HPLC). The radiochemical yields were 9–13% decay corrected (d.c.) with an average of 11% using K18F/kryptofix, and specific activity >2 GBq/µmol at the end of synthesis. The synthesis time was 67–75 min from the end of bombardment (EOB).