Development of an automated system for synthesizing 18F-labeled compounds using [18F]fluoroethyl bromide as a synthetic precursor

An automated system was developed to synthesize 18F-labeled compounds using [18F]fluoroethyl bromide ([18F]FEtBr) as a synthetic precursor. The apparatus makes possible the following sequence of processes: (1) production of an aqueous solution of [18F]fluoride ([18F]F−), (2) recovery of [18F]F− from target chamber, (3) drying of [18F]F−, (4) formation and distillation of [18F]FEtBr into a trapping vessel, (5) alkylation of target compounds with [18F]FEtBr, (6) High performance liquid chromatography purification and (7) formulation. [18F]FEtBr, the synthetic precursor for fluoroethylation, was labeled via nucleophilic displacement of 2-trifluoromethanesulfonyloxy ethylbromide (BrCH2CH2OTf) with [18F]F− and was purified from the reaction mixture by distillation. After the conditions for forming [18F]FEtBr and drying [18F]F− were optimized, [18F]FEtBr was obtained in a radiochemical yield of 71±13% (n=21, based on [18F]F−, corrected for decay) and a radiochemical purity of 98±1.4% at end of the syntheses (EOS). Using this automated system, [18F]fluoroethylspiperone ([18F]FEtSP) was prepared by reacting spiperone with [18F]FEtBr in a radiochemical yield and purity of 56±12% (n=5, based on [18F]FEtBr, corrected for decay) and 97±1.5% with a specific activity of 310±120 GBq/μmol at EOS. The total synthesis time was 55±2.3 min from the end of bombardment and the developed system has proved to be reliable and reproducible.