Facile synthesis of new carbon-11 labeled conformationally restricted rivastigmine analogues as potential PET agents for imaging AChE and BChE enzymes

Rivastigmine is a newer-generation inhibitor with a dual inhibitory action on both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes, and is used for the treatment of AChE- and BChE-related diseases such as brain Alzheimer's disease and cardiovascular disease. New carbon-11 labeled conformationally restricted rivastigmine analogues radiolabeled quaternary ammonium triflate salts, (3aR,9bS)-1-[C-11]methyl-1-methyl-6-(methylcarbarnoyloxy)-2,3,3a,4,5,9b-hexahydro-1H-benzo[g]indolium triflate ([C-11]8) and (3aR,9bS)-1-[C-11]methyl-1-methyl-6-(heptylcarbamoyloxy)-2,3,3a,4,5,9b-hexahydro-1H-benzo[g]indolium triflate ([C-11]9), were designed and synthesized as potential positron emission tomography (PET) agents for imaging AChE and BChE enzymes. The appropriate precursors were labeled with [C-11]CH3OTf through N-[C-11]lmethylation, and the target tracers were isolated by solid-phase extraction (SPE) using a cation-exchange CM Sep-Pak cartridge in 40-50% radiochemical yields decay corrected to end of bombardment (EOB), 15-20min overall synthesis time, and 148-222GBq/mu mol specific activity at EOB. (c) 2007 Elsevier Ltd. All rights reserved.