Synthesis and in vivo evaluation of (E)-N-[C-11]methyl-4-(3-pyridinyl)-3-butene-1-amine ([C-11]metanicotine) as a nicotinic receptor radioligand

(E)-N-[C-11]Methyl-4-(3-pyridinyl)-3-butene-1-amine ([C-11]metanicotine), a high affinity (K-i = 16 nM) CNS-selective nicotinic agonist, was prepared by the [C-11]alkylation of the desmethyl precursor with [C-11]methyl triflu oromethanesulfonate. In vivo distribution studies in mice demonstrated good blood brain permeability but essentially uniform regional brain distributi on and no evidence of specific binding to nicotinic cholinergic receptors. Identical results were obtained in an imaging study performed in a monkey b rain. Therefore, despite literature reports supporting the use of metanicot ine as a cognition enhancing nicotinic agonist, (E)-N-[C-11]methyl-4-(3-pyr idinyl)-3-butene-1-amine does not appear to be a suitable candidate for in vivo imaging studies of nicotinic acetylcholine receptors in the mammalian brain. NUCL MED BIOL 27;4:415-418, 2000. (C) 2000 Elsevier Science Inc. All rights reserved.