Mapping muscarinic receptors in human and baboon brain using [N‐¹¹C‐methyl]‐benztropine

The muscarinic cholinergic system has been mapped in vivo inhuman and baboon brain using [N‐¹¹C‐methyl]‐benztropine and high resolution positron emission tomography (PET). [N‐¹¹C‐methyl]‐benztropine uptake was observed in frontal, parietal, occipital, and temporal cortices as well as in subcortical structures including the corpus striatum and thalamus. Uptake continued to increase in baboon and human brain in all areas over an 80 minute experimental period with the exception of the exception of the cerebellum wehere the accumulation of radioactivity began to decrease by 25 minutes potinjection. The ratio of incorporation of [N‐¹¹C‐methyl]‐benztropine between corpus striatum/cerebellum was 1.53 and 1.46 in humans and baboons, respectively, at 60 minutes. Blocking studies in baboons using the muscarinic cholinergic antagonists scopolamine and benztropine and the muscarinic cholinergic agonist pilocarpine combined with blocking studies in humans using benztropine indicate that the binding of this compound is specific for the muscarinic cholinergic system. Pretreatment with the potent dopamine reuptake blocker nomifensine produced no effect on the incorporation of radioactivity in any baboon brain region examined. Analysis of labelled plasma metabolites indicates that in humans, the rate of metabolism of [N‐¹¹C‐methyl]‐benztropine is slow (83.0% unchanged at 30 minutes postinjection) differeing quite dramatically from the rate of metabolism observed in baboons (43.4%% unchanged at 30 minutes postinjection). These data combined with postmortem studies in humans and primates demonstrate that [N‐¹¹C‐methyl]‐benztropine is a suitablemuscarinic cholinergic ligand for use in humans and baboons with PET.