High-Yield Radiosynthesis and Preliminary In Vivo Evaluation of p-[18F]MPPF, a Fluoro Analog of WAY-100635

Abstract No-carrier-added 4-[ 18 F]fluoro- N -[2-[1-(2-methoxyphenyl)-1-piperazinyl]ethyl- N -2-pyridinyl-benzamide ( p -[ 18 F]MPPF) was synthesized by nucleophilic substitution of the corresponding nitro compound in the presence of Kryptofix 222 and K 2 CO 3 by microwave heating (3 min, 500 W) using a remotely controled radiosynthesis. Baseline separation of p -[ 18 F]MPPF from the nitro derivative was performed on a semipreparative HPLC C18 column. After Sep-Pak formulation, the radiopharmaceutical was obtained with a radiochemical yield of 25% (EOS) in about 70 min. Specific radioactivity averaged between 1–5 Ci/μmol EOS. Labelling of the ortho and meta derivatives was also attempted. Brain uptake of p -[ 18 F]MPPF was studied with PET on fluothane-anesthetized cats. Following intravenous injection of p -[ 18 F]MPPF, high accumulation of radioactivity was observed in the hippocampus and cerebral cortex. Low levels of radioactivity were observed in cerebellum. At 30 min, the mean hippocampus/cerebellum and cortex/cerebellum ratios were 5 and 3.8, respectively. The accumulation of the tracer was blocked by prior administration of reference WAY-100635, demonstrating the specificity of the ligand.