SYNTHESIS OF CARBON-11-LABELED AND FLUORINE-18-LABELED 1-METHYL-4-PIPERIDYL-4'-FLUOROBENZOATE AND THEIR BIODISTRIBUTION IN MICE

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