title: Carbon-11 labelled ketamine-synthesis, distribution in mice and PET studies in baboons.
abstract: No-carrier-added (NCA)[11C](+/-)-ketamine (2a) and its enantiomers (+)-2b and (-)-2c were synthesized by methylation of the corresponding norketamine (1a-c) with [11C]H3I in an overall radiochemical yield of 20% (EOB) with specific activities of 0.35-0.45 Ci/mumol at EOB in a synthesis time of 40 min from EOB. Compound 2a was metabolized rapidly in mouse brain and labeled metabolites appeared in baboon plasma. PET studies of compounds 2a-c in a baboon showed that influx of compounds 2a-c into the brain was high for the first few min but radioactivity then declined rapidly. Although the retention of radioactivity in the baboon striatum was not significantly different for 2a-c 20 min post-injection, graphical analysis of time-activity data for each enantiomer and for the racemate in baboon striatum suggested that (+)-ketamine may interact with receptors slightly more effectively than its (-)-enantiomer or racemate. However, due to its rapid metabolism in the brain and a similar uptake in the striatum and cerebellum, [11C]ketamine may not be an ideal tracer for studying NMDA receptor with PET.
authors.affiliation: Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973, USA.
authors.forename: C Y
authors.initials: CY
authors.lastname: Shiue
authors.forename: S
authors.initials: S
authors.lastname: Vallabhahosula
authors.forename: A P
authors.initials: AP
authors.lastname: Wolf
authors.forename: S L
authors.initials: SL
authors.lastname: Dewey
authors.forename: J S
authors.initials: JS
authors.lastname: Fowler
authors.forename: D J
authors.initials: DJ
authors.lastname: Schlyer
authors.forename: C D
authors.initials: CD
authors.lastname: Arnett
authors.forename: Y G
authors.initials: YG
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001692:Biological Transport; D001711:Biotransformation; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D007553:Isotope Labeling / Q000379:methods; D007649:Ketamine / Q000097:blood / Q000493:pharmacokinetics*; D051379:Mice; D008815:Mice, Inbred Strains; D010215:Papio; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods*
chemical_list: D002250:Carbon Radioisotopes; D007649:Ketamine