Synthesis and <i>ex vivo</i> evaluation of aza‐trozamicol analogs as SPECT radiotracers for exploration of the vesicular acetylcholine transporter

Abstract Several vesamicol derivatives have already been proposed for SPECT exploration of the vesicular acetylcholine transporter (VAChT) which is localized on the nerve endings of cholinergic neurons which are known to degenerate in the early stages of Alzheimer's disease. However, most of these tracers have disadvantages such as in vivo non‐specific binding, slow brain kinetics, or high toxicity. We present in this study the synthesis, the radiolabelling and the cerebral biodistribution in rats of two enantiomeric pairs of new trozamicol derivatives, potential imaging agents for the VAChT. Radiolabelled compounds were obtained with high purity and specific radioactivity. However, after i.v. injection in rats, they distributed homogeneously throughout the brain, in contrast to the reference compound IBVM which showed in the same experimental conditions a high striatum/cerebellum fixation ratio. These results demonstrate that these new compounds are unsuitable for the in vivo imaging of the VAChT using SPECT. Copyright © 2007 John Wiley &amp; Sons, Ltd.