Development of pre-synaptic cholinergic nervous system imaging agent for Alzheimer's disease early diagnosis

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We have tried to develop a molecular imaging agent of acethylcholine transporter (VAChT) for Alzheimer's disease early diagnosis, because biochemical changes of the presynaptic cholinergic system have been related to the pathogenesis of Alzheimer's disease. We synthesized (-)-[^<11>C]-methylvesamicol((-)-[^<11>C]OMV) and radioiodinated trans-decalin-o-iodovesamicol(DOIV) as new acetylcholine transporter imaging agents. (-)-[^<11>C]OMV binding in the ipsilateral cortex to the lesion was significantly reduced by 22.0±6.7% compared with that in the contralateral region in kinetics study using disability model monkeys produced by selectively destroying the p75NTR-positive cells in the right hemisphere of the brain. DOIV exhibited in vitro a highest affinity for VAChT among our vesamicol analogs synthesized previously. These results suggested that (-)-[^<11>C]OMV may be useful in the study of dementia characterized by degeneration of the cholinergic neurotransmitter system. Furthermore, radioiodinated DOIV may be superior to (-)-[^<11>C]OMV as VAChT imaging agent.