The potential of (-)-o-[11C]methylvesamicol for diagnosing cholinergic deficit dementia

Abstract

(-)-o-Methylvesamicol ((-)-OMV) exhibited in vitro a high affinity for a vesicular acetylcholine transporter (VAChT) (Ki, 6.7 nM), and (-)-o-[ 11C]methyl- vesamicol [(-)-[11C]OMV] exhibited appropriate kinetics and bound mainly to VAChTs in the rat brain. In this study, the in vivo distribution and kinetics of (- )-[11C]OMV were evaluated in comparison with [11C]SA4503 in disability model monkeys produced by selectively destroying the p75NTR-positive cells in the right hemisphere of the brain using positron emission tomography. Time-activity curves of (- )-[ 11C]OMV showed peaks within 20 min in regions rich in acetylcholine transporters (AchT). (-)- [111C]OMV binding in the ipsilateral cortex to the lesion was significantly reduced by 22.0% ± 6.7% when compared with that in the contralateral region. The decrease (19.3% ± 2.2%) in (-)-[11C]OMV binding in the ipsilateral temporal cortex to the lesion was greater than that (7.4% ± 4.6%) of [ 11C]SA4503. These results suggested that (-)-[11C]OMV may be useful in the study of dementia characterized by degeneration of the cholinergic neurotransmitter system. © 2008 Wiley-Liss, Inc.