title: Radiosynthesis and mouse brain distribution studies of [11C] CP-126,998: a PET ligand for in vivo study of acetylcholinesterase.
abstract: The selective, reversible acetylcholinesterase inhibitor 5,7-Dihydro-7-methyl-3- [2-[1-(phenylmethyl]-4-piperidinyl]ethyl]-6H-pyrrolo[3,2-f]-1,2-benzisoxazol3-6-one (CP-126,998) was labeled with C-11 iodomethane via base-promoted alkylation of the lactam nitrogen. [11C] CP-126,998 was synthesized in good radiochemical yield (13-29% non-decay corrected) and high specific radioactivity (177-418 GBq/micromol). In vivo mouse biodistribution studies reveal [11C] CP-126,998 to localize preferentially in striatal tissue, a region known to be rich in acetylcholinesterase. Competitive blocking studies using a variety of acetylcholinesterase inhibitors (diisopropylfluorophosphate, tacrine, CP-118,954) verified the specificity of the PET radiotracer for brain acetylcholinesterase.
authors.affiliation: Johns Hopkins University School of Medicine, Department of Radiology, Division of Nuclear Medicine, Baltimore, MD 21287, USA. jlmusachio@petscan.nm.jhu.edu
authors.forename: John L
authors.initials: JL
authors.lastname: Musachio
authors.forename: John E
authors.initials: JE
authors.lastname: Flesher
authors.forename: Ursula A
authors.initials: UA
authors.lastname: Scheffel
authors.forename: Paige
authors.initials: P
authors.lastname: Rauseo
authors.forename: John
authors.initials: J
authors.lastname: Hilton
authors.forename: William B
authors.initials: WB
authors.lastname: Mathews
authors.forename: Hayden T
authors.initials: HT
authors.lastname: Ravert
authors.forename: Robert F
authors.initials: RF
authors.lastname: Dannals
authors.forename: J James
authors.initials: JJ
authors.lastname: Frost
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics*; D007531:Isoflurophate / Q000494:pharmacology; D007553:Isotope Labeling / Q000379:methods; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D008024:Ligands; D008297:Male; D051379:Mice; D010880:Piperidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D012016:Reference Values; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
chemical_list: C461520:CP 126,998; D002250:Carbon Radioisotopes; D007555:Isoxazoles; D008024:Ligands; D010880:Piperidines; D019275:Radiopharmaceuticals; D007531:Isoflurophate; D000110:Acetylcholinesterase