title: N-[18F]fluoroethyl-4-piperidyl acetate ([18F]FEtP4A): A PET tracer for imaging brain acetylcholinesterase in vivo.
abstract: N-[(18)F]Fluoroethyl-4-piperidyl acetate ([(18)F]FEtP4A) was synthesized and evaluated as a PET tracer for imaging brain acetylcholinesterase (AchE) in vivo. [(18)F]FEtP4A was previously prepared by reacting 4-piperidyl acetate (P4A) with 2-[(18)F]fluoroethyl bromide ([(18)F]FEtBr) at 130 degrees C for 30 min in 37% radiochemical yield using an automated synthetic system. In this work, [(18)F]FEtP4A was synthesized by reacting P4A with 2-[(18)F]fluoroethyl iodide ([(18)F]FEtI) or 2-[(18)F]fluoroethyl triflate ([(18)F]FEtOTf in improved radiochemical yields, compared with [(18)F]FEtBr under the corresponding condition. Ex vivo autoradiogram of rat brain and PET summation image of monkey brain after iv injection of [(18)F]FEtP4A displayed a high radioactivity in the striatum, a region with the highest AchE activity in the brain. Moreover, the distribution pattern of (18)F radioactivity was consistent with that of AchE in the brain: striatum>frontal cortex>cerebellum. In the rat and monkey plasma, two radioactive metabolites were detected. However, their presence might not preclude the imaging studies for AchE in the brain, because they were too hydrophilic to pass the blood-brain barrier and to enter the brain. In the rat brain, only [(18)F]fluoroethyl-4-piperidinol ([(18)F]FEtP4OH) was detected at 30 min postinjection. The hydrolytic [(18)F]FEtP4OH displayed a slow washout and a long retention in the monkey brain until the PET experiment (120 min). Although [(18)F]FEtP4A is a potential PET tracer for imaging AchE in vivo, its lower hydrolytic rate and lower specificity for AchE than those of [(11)C]MP4A may limit its usefulness for the quantitative measurement for AchE in the primate brain.
authors.affiliation: Department of Medical Imaging, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan. zhang@nirs.go.jp
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
authors.forename: Kenji
authors.initials: K
authors.lastname: Furutsuka
authors.forename: Jun
authors.initials: J
authors.lastname: Maeda
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Takayo
authors.initials: T
authors.lastname: Kida
authors.forename: Takashi
authors.initials: T
authors.lastname: Okauchi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Irie
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000085:Acetates / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging* / Q000201:enzymology*; D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D006868:Hydrolysis; D008253:Macaca mulatta; D008297:Male; D010880:Piperidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000138:chemical synthesis; D051381:Rats; D012680:Sensitivity and Specificity; D014055:Tomography, Emission-Computed
chemical_list: D000085:Acetates; D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; C469347:N-fluoroethyl-4-piperidyl acetate; C100518:N-methyl-4-piperidyl acetate; D010880:Piperidines; D019275:Radiopharmaceuticals; D000110:Acetylcholinesterase