title: Carbon-11 N-methyl alkylation of L-368,899 and in vivo PET imaging investigations for neural oxytocin receptors.
abstract: Compound L-368,899 was successfully alkylated with [(11)C]iodomethane to generate the oxytocin receptor selective (2R)-2-amino-N-((2S)-7,7-dimethyl-1-(((4-(o-tolyl)piperazin-1-yl)sulfonyl)methyl)bicyclo[2.2.1]heptan-2-yl)-N-[(11)C]methyl-3-(methylsulfonyl)propanamide ([(11)C]1) with very high radiochemical purity and high specific activity. PET imaging studies were performed with [(11)C]1 to investigate brain penetration and oxytocin receptor uptake using rat and cynomolgus monkey models. For rat baseline scans, brain penetration was observed with [(11)C]1, but no specific uptake could be distinguished in the brain region. By administering a peptide oxytocin receptor selective antagonist for peripheral blocking of oxytocin receptors, the uptake of [(11)C]1 was amplified in the rat brain temporarily to enable some visual uptake within the rat brain. A baseline scan of [(11)C]1 in a cynomolgus monkey model resulted in no detectable specific uptake in anticipated regions, but activity did accumulate in the choroid plexus.
authors.affiliation: Center for Translational Social Neuroscience, Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Atlanta, GA 30322, USA.
authors.forename: Aaron L
authors.initials: AL
authors.lastname: Smith
authors.forename: Sara M
authors.initials: SM
authors.lastname: Freeman
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Voll
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Young
authors.forename: Mark M
authors.initials: MM
authors.lastname: Goodman
mesh_terms: D000478:Alkylation; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging*; D001892:Camphanes / Q000737:chemistry*; D002250:Carbon Radioisotopes / Q000737:chemistry*; D008252:Macaca fascicularis; D023421:Models, Animal; D015394:Molecular Structure; D010879:Piperazines / Q000737:chemistry*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D051381:Rats; D018045:Receptors, Oxytocin / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000378:metabolism*
chemical_list: D001892:Camphanes; D002250:Carbon Radioisotopes; D010879:Piperazines; D019275:Radiopharmaceuticals; D018045:Receptors, Oxytocin; C086206:L 368899