An attempt to visualize baboon brain nicotinic receptors with N-[11C]ABT-418 and N-[11C]methyl-cytisine.

ABT-418 ((S)-3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole) and N-methyl-cytisine, high-affinity nicotinic cholinergic agonists, were labelled with 11C and evaluated in vivo using positron emission tomography (PET) for the visualization of nicotinic cholinergic receptors in baboon brain. Both labelled compounds were synthesized by methylation to their respective precursors, A-79814 and cytisine, using [11C]methyliodide. Following the intravenous (i.v.) injection of N-[11C]ABT-418, uptake in brain was rapid but low, with a peak at 1-2 min (4.40 +/- 0.2% of injected dose per 100 ml tissue) followed by rapid washout. Clearance of radioactivity from the blood was rapid. The regional distribution of the radioactivity followed mainly the distribution of grey matter. Slightly lower uptake in the cerebellum than in the cortex was observed. The uptake and the shape of the time-activity curves were unchanged following the co-administration of labelled and of excess (1 mumol kg-1) unlabelled ABT-418. Thus the essential criteria for visualizing receptor binding with PET could not be fulfilled. Following the i.v. injection of N-[11C]methyl-cytisine, the activity in the brain was not significantly different from that of blood (0.86 +/- 0.01% and 0.96 +/- 0.1% of injected dose per 100 ml tissue, respectively). Thus N-[11C]ABT-418 and N-[11C]methylcytisine do not appear to be suitable tracers for PET studies of nicotine cholinergic receptors in primate brain.