In vitro and In vivo evaluation of Radioiodinated (-) -m-iodovesamicol : Potential radioligand for diagnosing Alzheimer's disease.

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The purpose of this investigation is to develop a new presynaptic cholinergic neuron mapping agent. We synthesized levorotatory isomer (-) -m-iodovesamicol ((-) mIV) radioiodinated at the meta position of the 4-phenylpiperidine moiety and evaluated the in vitro and in vivo binding affinity and specificity of [I-125] (-) -mIV for the vesamicol receptor in rat brain, furthermore, evaluated the in vivo characteristics of [I-125] (-) -mIV in the model rat of Alzheimer's disease. In vitro and In vivo binding affinity of [I-125] (-) -mIV for the vesamicol receptor (acetylcholine transporter) was very high and comparable to that of (-) -vesamicol ; the binding affinity for dopamine, serotonin, noradrenaline, acetylcholine and sigma receptors was low. These similar results were derived from saturation binding study ; Kd (18.2nM) and Bmax (660 fmol/mg of protein) of [I-125] (-) -mIV were comparable to those of (-) -vesamicol (Kd=20-30nM,Bmax=334-516fmol/mg of protein). Furthermore, double-tracer autoradiograms using [I-125] (-) -mIV and [Tc-99m] HMPAO in model rat brain of Alzheimer's disease showed a significant 11% decrease of the accumulation of [I-125] (-) -mIV in the projection cortices ipsilateral to the basalforebrain lesion in a unilateral cholinergic denervation model, which is regarded as an experimental model of Alzheimer's disease. The difference between the decrease of the accumulation of [I-125] (-) -mIV (11%) and that of [Tc-99m] HMPAO (4%) in the regions was statistically significant (P<0.01). These results suggest that radioiodinated (-) -mIV may serve as a useful radioligand for mapping presynaptic cholinergic neurons.