Carbon-11 labelled ketamine-synthesis, distribution in mice and PET studies in baboons.
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.
Shiue
C Y
CY
Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973, USA.
Vallabhahosula
S
S
Wolf
A P
AP
Dewey
S L
SL
Fowler
J S
JS
Schlyer
D J
DJ
Arnett
C D
CD
Zhou
Y G
YG
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*
D002250:Carbon Radioisotopes; D007649:Ketamine