Synthesis of carbon-11- and fluorine-18-labeled 1-methyl-4-piperidyl-4'-fluorobenzoate and their biodistribution in mice.

ABSTRACT

Carbon-11- and fluorine-18-labeled forms of 1-methyl-4-piperidyl-4'-fluorobenzoate were prepared as potential in vivo substrates for brain acetylcholinesterase. The 1-methyl-4-piperidyl-4'-[18F]fluorobenzoate was prepared by aromatic nucleophilic substitution using the nitro precursor and no-carrier added [18F]fluoride ion. The 1-[11C]methyl-4-piperidyl-4'-fluorobenzoate was synthesized by N-[11C]methylation of the appropriate nor-methyl precursor. Biodistribution studies in mice showed high brain uptake of these radiotracers followed by a fast washout with no significant retention of radioactivity in areas of high acetylcholinesterase enzymatic activity. This is contrasted with 1-[11C]methyl-4-piperidylacetate, which is rapidly trapped in brain tissues through hydrolysis by AChE. Further in vivo and in vitro studies demonstrated that 1-methyl-4-piperidyl-4'-fluorobenzoate was not a substrate for AChE, and thus not suitable as an in vivo radiotracer for studying this enzyme in the brain.