Radiosynthesis and PET studies of [C-11]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-ii using [C-11]methyl iodide via a simple and efficient one-step procedure. Regioselectivity of [C-11]methylation on the aliphatic nitrogen versus pyridine nitrogen is strongly dependent on t he reaction solvent. The reaction in acetonitrile exclusively yields alipha tic N-[C-11-methyl]alkylation ([C-11]RJR-2403), while only a byproduct is f ormed when DMF is used as a solvent. Positron emission tomographic (PET) st udies in baboon showed a homogeneous distribution of radioactivity within b aboon brain with a slow clearance. [C-11]RJR-2403 was metabolized very rapi dly as evidenced by the fact that at 2 min after intravenous injection only 50% of the total carbon-ii in plasma is parent compound. Copyright (C) 200 1 John Wiley & Sons, Ltd.