2-[18F]F-A-85380:: a PET radioligand for α4β2 nicotinic acetylcholine receptors

2-[F-18]FLUORO-3-(2(S)-AZETIDINYMETHOXY)PYRIDINE (2[F-18]F-A-85380), a ligand for nicotinic acetylcholine receptors (nAChRs) was evaluated in an in vitro binding assay with membranes of rat brain and in vivo by PET in Rhesus monkey brain. The ligand has high affinity for alpha(4)beta(2) nAChRs (K-D=50pM), crosses the blood-brain barrier, and distributes in the monkey brain in a pattern consistent with that of alpha(4)beta(2) nAChRs. The specific/non-specific binding ratio increased steadily, reaching a value of 3.3 in the thalamus at 4 h. The specific binding of 2-[F-18]F-A-85380 Was reversed by cytisine. These results, in combination with the data demonstrating low toxicity of 2-[F-18]F-A-85380, indicate that this ligand shows promise for use with PET in human subjects. (C) 1999 Lippincott Williams & Wilkins.