Synthesis and In-Vivo Evaluation of [<sup>11</sup>C]p-PVP-MEMA as a PET Radioligand for Imaging Nicotinic Receptors.


Within the class of (4-pyridinyl)vinylpyridines developed by Abbott labs. as potent neuronal nicotinic acetylcholine receptor ligands, p-PVP-MEMA ({(R)-2-[6-chloro-5-((E)-2-pyridin-4-ylvinyl)pyridin-3-yloxy]-1-methylethyl}methylamine) is the lead compd. of a novel series that do not display the traditional nicotinic-like pyrrole-ring but still possessing high subnanomolar affinity (Ki 0.077 nm-displacement of 3Hcytisine from whole rat brain synaptic membranes). In the present study, p-PVP-MEMA and its nor-deriv. ({(R)-2-[6-chloro-5-((E)-2-pyridin-4-ylvinyl)pyridin-3-yloxy]-1-methylethyl}methylamine) as precursor for labeling with the short-lived positron-emitter carbon-11 (T12 20.4 min) were synthesized in 10 chem. steps from 2-hydroxy-5-nitropyridine and Boc-D-alanine. N-Alkylation of nor-p-PVP-MEMA with [11C]methyl iodide afforded [11C]p-PVP-MEMA (>98% radiochem. pure, specific activity of 86.4 GBq μmol-1) in 2% (non-decay cor. and non-optimized) radiochem. yield, in 34 min (including HPLC purifn. and formulation). Preliminary positron emission tomog. (PET) results obtained in a Papio hamadryas baboon showed that [11C]p-PVP-MEMA is not a suitable PET-radioligand.

Australian Journal of Chemistry