C-11 LABELED KETAMINE - SYNTHESIS, DISTRIBUTION IN MICE AND PET STUDIES IN BABOONS

No carrier-added (NCA)[C-11](+/-)-ketamine (2a) and its errantiomers ( +)-2b and (-)-2e were synthesized by methylation of the corresponding norketamine (1a-c) with [C-11]H3I in an overall radiochemical yield of 20% (EOB) with specific activities of 0.35-0.45 Ci/mu mole at EOB in a synthesis time of 40 min from EOB. Compound 2a was metabolized rapid ly in mouse brain and labeled metabolites appeared in baboon plasma. P ET studies of compounds 2a-c in a baboon showed that influx of compoun ds 2a-c into the brain was high for the first few min but radioactivit y then declined rapidly. Although the retention of radioactivity in th e baboon striatum was not significantly different for 2a-c 20 min post injection, graphical analysis of time-activity data for each enantiom er and for the racemate in baboon striatum suggested that (+)-ketamine may interact with receptors slightly more effectively than its (-)-en antiomer or racemate. However, due to its rapid metabolism in the brai n and a similar uptake in the striatum and cerebellum, [C-11]ketamine may not be an ideal tracer for studying NMDA receptor with PET. (C) 19 97 Elsevier Science Inc.