In vivo investigation of brain nicotine receptors using optically active radioligand

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Changes in the density of nicotinic receptors have recently been reported in the brains of patients with various disorders, including Alzheimer's disease. These observations have stimulated interest in means of imaging the distribution of nicotinic receptors noninvasively in vivo with nuclear medicinal imaging techniques such as SPECT.In this study, the superior radiation properties of 123-I for SPECT promoted us to syntheszed a radioiodinated nicotine anlog iodinated at the 5-position of the pyridine, was synthesized and evaluated as a potential radioligand for investigating brain nicotine receptors by SPECT.Radioiodinated (S)-5-iodonicotine (INC) was synthsized by the radiodestannylation reaction under no-carrier-added conditions. The binding affinity of INC for brain nicotine receptors was measured in terms of displacement of 3-H-cytisine from binding sites in rat cortical membranes. The binding data revealed that the affinity of INC was the same as that of (S)-nicotine and 80-fold … More higher than that of the (R)-enatiomer. Regional cerebral distribution studies in rats by autoradiography disclosed that the accumulation of 125-I-INC was dense in the thalamus, intermediate in the cortex and striatum, and less marked in the cerebellum. 125-I-(R)-INC showed more rapid washout from the brain and less extensive regional cerebral distribution than the (S)-enatiomer. Gathered data indicate that 123-I-labeled (S)-INC is a potential radioligand for use in vivo cerebral nicotinic receptor studies by SPECT.Furthermore, the influence of inhibition of cholinergic projection on the nicotinic receptor function was investigated using quantitative autoradiography with 125-I-INC.Regional cerebral distribution of 125-I-INC was evaluated after selective inhibition of cholinergic neurons in rat basal forbrain using pyruvate dehydrogenase complex inhibitor, 3-bromopyruvic acid (BPA). In ipsilateral cortex, INC uptake increased at 6 hr post surgery and significantly decreased at 7days. The results indicate that nicotine receptor function in cerebral cortex changes after the legion of the basal forebrain. Less