N-[18F]fluoroethylpiperidin-4-ylmethyl butyrate: a novel radiotracer for quantifying brain butyrylcholinesterase activity by positron emission tomography

In Alzheimerʹs disease, cerebral cortical butyrylcholinesterase (BChE) activity is reported to be elevated. Our aim was to develop a novel 18F-labeled tracer for quantifying cerebral BChE activity by positron emission tomography. With in vitro screening of N-[14C]ethylpiperidin-3- and 4-ylmethyl esters, N-[14C]ethylpiperidin-4-ylmethyl butyrate was selected as a lead for 18F-labeling, affording N-[18F]fluoroethylpiperidin-4-ylmethyl butyrate. The 18F-labeled butyrate showed the required properties for in vivo BChE measurement, that is, the lipophilic nature of the authentic ester, high specificity to BChE, a moderate hydrolysis rate, and the hydrophilic nature of the metabolite.