Syntheses and biological evaluation of ¹⁸F-labeled 3-(1-benzyl- piperidin-4-yl)-1-(1-methyl-1H-indol-3-yl)propan-1-ones for in vivo mapping of acetylcholinesterase

We synthesized novel ¹⁸F-labeled acetylcholinesterase (AChE) inhibitors, 3-[1-(3- and 4-[¹⁸F]fluoromethylbenzyl)piperidin-4-yl]-1-(1- methyl-1H-indol-3-yl)propan-1-ones ([¹⁸F]1 and [¹⁸F]2) and 3-[1-(4- [¹⁸F]fluorobenzyl)piperidin-4-yl]-1-(1-methyl-1H-indol-3-yl)propan-1-one ([¹⁸F]3) in high yields (decay-corrected, 25%-40%) and with high effective specific activities (>37 GBq/μmol). Tissue distribution studies of the [¹⁸F]1 and the [¹⁸F]3 in mice showed the nonspecific bindings in brain regions, with metabolic defluorination of the [¹⁸F]1. The result suggests that these radioligands may not be suitable agents for in vivo mapping of AChE, despite their potent in vitro anti-AChE activities. (C) 2000 Elsevier Science Inc.