(S)- and (R)-[11C]nicotine and the metabolite (R/S)-[11C]cotinine. Preparation, metabolite studies and in vivo distribution in the human brain using PET

Int J Rad Appl Instrum B. 1992 Nov;19(8):871-80. doi: 10.1016/0883-2897(92)90173-v.


In order to investigate [11C]nicotine binding and metabolism in the living human brain by PET, routine protocols were developed for the preparation and purification of (S)- and (R)-[11C]nicotine and the metabolite (R/S)-[11C]cotinine. (S)- and (R)-[11C]nicotine were prepared by N-methylation with [11C]methyl iodide of the appropriate secondary amine, which was liberated in situ by 2,2,6,6,-tetramethylpiperidine (TMP) from its corresponding biscamsylate-salt. (R/S)-[11C]Cotinine was prepared by N-methylation of the amide precursor using tetrabutylammonium hydroxide as a phase transfer catalyst. Straight-phase semipreparative HPLC was in all purifications found to be superior to reversed-phase since the contamination by the norcompounds was eliminated. Reaction in acetonitrile for both (S)- and (R)-[11C]nicotine (5 min, 130 degrees C) and (R/S)-[11C]cotinine (1 min, 80 degrees C) with subsequent straight-phase HPLC purification resulted in 35-45% radiochemical yield (from EOB and decay-corrected) with a total synthesis time of 30-35 min, a specific radioactivity of 1000-1500 Ci/mmol (37-55 GBq/mumol, EOS) and a radiochemical purity > 99%. The uptake and distribution of these tracers in the human brain was studied in healthy volunteers by PET. The metabolite (R/S)-[11C]cotinine did not cross the blood-brain barrier to any significant degree. The amount of the total radioactivity representing (S)-[11C]nicotine measured in plasma by HPLC was 75% at 4 min and 25% at 50 min.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / metabolism*
  • Carbon Radioisotopes*
  • Cotinine / metabolism*
  • Humans
  • Male
  • Nicotine / metabolism*
  • Quality Control
  • Stereoisomerism
  • Tomography, Emission-Computed*


  • Carbon Radioisotopes
  • Nicotine
  • Cotinine