Current Topics in Medicinal Chemistry

Allen B. Reitz
Fox Chase Chemical Diversity Center, Inc.
Doylestown, PA
USA

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PET Radioligands for the Vesicular Acetylcholine Transporter (VAChT)

Author(s): Nicolas Giboureau, Ian Mat Som, Aurelie Boucher-Arnold, Denis Guilloteau and Michael Kassiou

Affiliation: Brain and Mind Research Institute, 100 Mallett Street, Camperdown, NSW 2050 Australia.

Keywords: VAChT, Alzheimer's disease, benzovesamicol, positron emission tomography, fluorine-18, carbon-11, PET

Abstract:

The vesicular acetylcholine transporter (VAChT) is a glycoprotein responsible for the accumulation of acetylcholine into pre-synaptic vesicules of cholinergic neurons. Cholinergic innervation has been shown to be decreased at the earlier stages of Alzheimers disease (AD). Thus, the expression of VAChT has been correlated with the severity of the dementia and has been considered as a significant diagnostic target for AD. To this end numerous radioligands based on the vesamicol scaffold have been developed for imaging the VAChT using positron emission tomography (PET). Among the various radioligands only a small number have been evaluated in vivo in non-human primate and human. Despite promising in vitro, ex vivo and first in vivo studies, most of them are unsuitable for clinical use in humans due to poor selectivity over σ receptors, low extraction from the blood, slow brain kinetics or fast metabolism. To date (-)-[11C]OMV (1), (-)-[11C]MABV (2), (-)-[18F]-FEOBV (6), (-)-trans-2-hydroxy-3-(4-(4-[18F]fluorobenzoyl)piperidine) tetralin (8) and [18F]FBMV (12) are promising radioligands for the VAChT, though further validation is required to confirm their clinical usefulness.

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Article Details

VOLUME: 10
ISSUE: 15
Page: [1569 - 1583]
Pages: 15
DOI: 10.2174/156802610793176846