title: Comparison of N-[(11)C]methyl-norchloroepibatidine and N-[(11)C]methyl-2-(2-pyridyl)-7-azabicyclo[2.2.1]heptane with N-[(11)C]methyl-epibatidine in small animal PET studies.
abstract: Structural variations of the nicotinic acetylcholine receptor radioligand N-[(11)C]methyl-epibatidine were made to form (11)C-labeled N-methyl-norchloroepibatidine (N-methyl-NorchloroEPB) and N-methyl-2-(2-pyridyl)-7-azabicyclo[2.2.1]heptane (N-methyl-2PABH). Radiosyntheses were performed by methylation with high radiochemical purities (>98%) and with specific activities between 140 and 500 GBq/micromol at the end of synthesis. The radiochemical yield (decay-corrected, related to [(11)C]CH(3)I) was between 5 and 10%. Positively and negatively radiolabeled enantiomers were prepared in high optical purity (>98%ee) by labeling of the appropriate optically active substrates, which were obtained via chiral high performance liquid chromatography. For in vivo studies radioligands were administered intravenously in rats. Brain uptake curves were acquired and combined with blocking experiments. Brain uptake of N-[(11)C]methyl-NorchloroEPB was similar to that of N-[(11)C]methyl-EPB whereas N-[(11)C]methyl-2PABH with the modified pyridine ring had a significantly lower uptake.
authors.affiliation: Center for Radiopharmaceutical Science, Swiss Federal Institute of Technology, Paul Scherrer Institute and University Hospital of Zürich, Zurich, Switzerland.
authors.forename: J E
authors.initials: JE
authors.lastname: Spang
authors.forename: J T
authors.initials: JT
authors.lastname: Patt
authors.forename: G
authors.initials: G
authors.lastname: Westera
authors.forename: P A
authors.initials: PA
authors.lastname: Schubiger
mesh_terms: D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000493:pharmacokinetics; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D003596:Cytosine / Q000378:metabolism; D007275:Injections, Intravenous; D008055:Lipids / Q000737:chemistry; D008297:Male; D011725:Pyridines / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed; D014915:Whole-Body Counting
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D008055:Lipids; C413490:N-methyl-2PABH; C413489:N-methyl-norchloroEPB; D011725:Pyridines; D019275:Radiopharmaceuticals; D003596:Cytosine