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-[(11)C]methyl-1-methyl-6-(methylcarbamoyloxy)-2,3,3a,4,5,9b-hexahydro-1H-benzo[g]indolium triflate ([(11)C]8) and (3aR,9bS)-1-[(11)C]methyl-1-methyl-6-(heptylcarbamoyloxy)-2,3,3a,4,5,9b-hexahydro-1H-benzo[g]indolium triflate ([(11)C]9), were designed and synthesized as potential positron emission tomography (PET) agents for imaging AChE and BChE enzymes. The appropriate precursors were labeled with [(11)C]CH(3)OTf through N-[(11)C]methylation, 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), 15-20 min overall synthesis time, and 148-222 GBq/micromol specific activity at EOB.
D000110:Acetylcholinesterase / Q000032:analysis*; D002091:Butyrylcholinesterase / Q000032:analysis*; D002250:Carbon Radioisotopes / Q000737:chemistry*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D006331:Heart Diseases / Q000000981:diagnostic imaging / Q000201:enzymology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D048448:Phenylcarbamates / Q000138:chemical synthesis* / Q000737:chemistry; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D000068836:Rivastigmine
D002250:Carbon Radioisotopes; D002800:Cholinesterase Inhibitors; D048448:Phenylcarbamates; D019275:Radiopharmaceuticals; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D000068836:Rivastigmine