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/mumol 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.

Synthesis and preliminary evaluation of [18F]FEtP4A, a promising PET tracer for mapping acetylcholinesterase in vivo.

N-[18F]Fluoroethyl-4-piperidyl acetate ([18F]FEtP4A), an analog of [11C]MP4A for mapping brain acetylcholineseterase (AchE) activity, was prepared by reacting 4-piperidyl acetate (P4A) with [18F]fluoroethyl bromide ([18F]FEtBr) using a newly developed automated system. Preliminary evaluation showed that the initial uptake of [18F]FEtP4A in the mouse brain was > 8% injected dose/g tissue. The distribution pattern of [18F]FEtP4A in the brain was striatum>cerebral cortex>cerebellum within 10-120 min post-injection, which reflected the distribution rank pattern of AchE activity in the brain. Moreover, chemical analysis of in vivo radioactive metabolites in the mouse brain indicated that 83% of [18F]FEtP4A was hydrolyzed to N-[18F]fluoroethyl-4-piperidinol ([18F]FEtP4OH) after 1 min intravenous injection. From these results, [18F]FEtP4A may become a promising PET tracer for mapping the AchE in vivo.