Research on Brain Function through in vivo Neuroreceptor Study Using Positron Emission Tomography

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In order to make clear the mechanisms of brain function,we examined the receptor binding in various receptor system in the brain and obtained the following results.1. Using C-11 SCH23390 as a dopamine D1 ligand,we established a method for quantification of binding capacity using positron emission tomography (PET). The binding capacity was measured in healthy volunteers and age-related decrease of the binding was observed both in the striatum and frontal cortex. The binding was also measured in patients with mood disorders and decrease of the binding was observed only in the frontal cortex but not in the striatum.2. C-11 Ro15-1788, a ligand of central type benzodiazepine receptor, was administered to normal volunteers with or without non-radioactive carrier. In vivo Scachard analysis was made using the value of specific binding measured by PET and serum activity of free ligand and Bmax and KD value of benzodiazepine receptor in the human brain was calculated.3. We developed C-11 benztropin as a ligand of acetylcholine receptor. The first imaging study with the tracer was performed using PET. The radioactivity was high in the striatum and thalamus, where receptor density was high. On the other hand, the radioactivity in the cerebellum, where receptor density was low. Using the image data and serum activity of free ligand, a method of quantification is under developing.4. Binding of benzodiazepine receptor was measured in senile accelerated mouse (SAM) in relation to increasing of age. Age-related decrease of the binding to the cortex was observed in control R/1 line, whereas the decrease was not observed in prone P/8 line.