Evaluation of radioiodinated (-)-o-iodovesamicol as a radiotracer for mapping the vesicular acetylcholine transporter.

We evaluated the potencies of radioiodinated (-)-o-iodovesamicol [(-)-oIV] as a selective vesicular acetylcholine transporter (VAChT) mapping agent. (-)-[125I]oIV exhibited significant accumulation (about 2.8% of the injected dose) in rat brain. The regional brain distribution of radioactivity was similar for both (-)-[125I]olV and (-)-[3H]vesamicol. The accumulation of (-)-[125I]oIV in the brain was significant reduced by post-administration of unlabeled vesamicol (0.5 /micromol/kg(-1)) and (-)-oIV (0.5 micromol/kg(-1)). On the other hand, the post-administration of sigma ligands hardly affected the accumulation of (-)-[125I]oIV in the brain. These studies showed that (-)-[125I]oIV, as well as [3H] vesamicol, bound to VAChT with high affinity in the rat brain. Furthermore, (-)-[125I]oIV binding in the ipsilateral cortex to the lesion was significantly reduced by 17.0%, compared with that in the contralateral cortex in a unilateral NBM-lesioned rat. These results suggested that radioiodinated (-)-oIV may potentially be useful for the diagnosis of cholinergic neurodegenerative disorders.