Biochemical changes in postmortem brains of Alzheimer s diseaase patients include decreased acetylcholinesterase and choline acetyl transferase activity, indicating reduced activity of the central cholinergic system, while butyrylcholinesterase (BChE) activity increases. A method that can measure regional BChE activity in the brain in vivo may be useful for investigation the relationship between BChE and Alzheimer s disease. Seven compounds, either piperidinyl or pyrrolidinyl butyrates, were synathesized as BChE substrate radiotracers to map central BChE activity in vivo by positron emission tomography (PET). 14C-labeled compounds were assayed to determine their hydrolysis rates by BChE and the partition coefficient. The five esters of secondary alcohols had lipophilic properties sufficient to pass readily through the blood-brain barrier while the metabolites were sufficiently hydrophilic to be retained in the brain. The esters showed moderate hydrolysis rates by BChE and high specificity for BChE relaative to acetylcholinesterase, while two esters of primary alcohols were hydrolyzed too rapidly to estimate reliably the local cerebral BChE activity. From these results, we conclude that one or more of these five esters, when labeled with 11C, would be a useful racer for quantigication of BChE activity by PET
