Radiosynthesis of 6-([¹⁸F]fluoroacetamido)-1-hexanoic-anilide ([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).