Radiosynthesis and PET studies of [ 11 C]RJR‐2403, a nicotinic agonist

(E)‐ N ‐methyl‐4‐(3‐pyridinyl)‐3‐butene‐1‐amine (RJR‐2403, or metanicotine), a nicotinic agonist developed as a cognitive‐enhancing drug for Alzheimer's disease, was labeled with carbon‐11 using [ 11 C]methyl iodide via a simple and efficient one‐step procedure. Regioselectivity of [ 11 C]methylation on the aliphatic nitrogen versus pyridine nitrogen is strongly dependent on the reaction solvent. The reaction in acetonitrile exclusively yields aliphatic N‐[ 11 C‐methyl]alkylation ([ 11 C]RJR‐2403), while only a byproduct is formed when DMF is used as a solvent. Positron emission tomographic (PET) studies in baboon showed a homogeneous distribution of radioactivity within baboon brain with a slow clearance. [ 11 C]RJR‐2403 was metabolized very rapidly as evidenced by the fact that at 2 min after intravenous injection only 50% of the total carbon‐11 in plasma is parent compound. Copyright © 2001 John Wiley & Sons, Ltd.