The potential radioiodinated (-)-o-iodovesamicol for diagnosing-Alzhemer's disease.

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We evaluated the potencies of radioiodinated (-)-o-iodovesamicol [(-)-oIV] as a selective vesicular acetylcholine transporter (VAChT) mapping agent. In vitro studies, (-)-enantiomers [(-)-ortho-iodovesamicol ((-)-OIV), (-)-meta-iodovesamicol ((-)-mIV), (-)-vesamicol] displayed a higher affinity for VAChT than (+)-enantiomer [(+)-OIV, (+)mlV, (+)-vesamicol]. (-)-OIV and (-)-mlV showed the same high affinity for VAChT as (-)-vesamicol. For sigma receptors(σ-1, σ-2), (-)-OIV (Ki = 62.2 nM ( to σ-1) and 554 nM ( to σ-2 ) ) showed a lower affinity than (-)-mlV ( Ki = 4.5 nM ( to σ-1) and 42.9 nM (to σ-2 ) ). In vivo regional brain distribution study and ex vivo autoradiographic study, the characteristics of (-)-[^<125>I]oIV accumulation is very similar to that of [^3H]vesamicol in rat brain. Displacement studies in vivo showed that the binding affinity of (-)[^<125>I]oIV for VAChT was very high and that for sigma receptors was low. Furthermore, the rate of reduction in (-)-[^<125>I]oIV accumulation (17 %) was significantly higher than that of (-) [^<125>I]mIV (10 %) in the ipsilateral cortex to the lesion (P < 0.01) in a unilateral NBM-lesioned rat. These results suggested that (-)-OIV is superior to (-)mlV as a selective vesicular acetylcholine transporter mapping agent. Radioiodinated (-)-oIV may potentially be useful for diagnosis of Alzheimer's disease.