| Co-Investigator(Kenkyū-buntansha) |
FUKUYAMA Hideano Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (90181297)
SAJI Hideo Kyoto University, Graduate School of Phartology, Proffessor, 薬学研究科, 教授 (40115853)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
Neuronal nicotinic acetylcholine receptors (nAChRs) are widely distributed in the human brain. Recently, 5-iodo-3-(2S)-azetidinylmethoxy) pyridine (5IA) has been synthesized as a radioligand for imaging nAChRs with SPECT. The purpose of this study was to establish the quantitative measurements of nAChR binding by using 5IA SPECT and apply it to Parkinson's disorders.
In the healthy volunteers, a 6-h dynamic SPECT acquisition was performed just after an I-123 5IA injection. Arterial blood samplings were done and pure 5IA concentrations were obtained by the TLC as input function. Two-compartment model (2C) and Logan plot were applied for kinetic analysis. Two scans were done in the smoking healthy volunteers, one was under smoking state and another was after 20-days smoke-free period. In the second, we performed 5IA SPECT studies in the patients with Parkinson's disease (PD).
Good relationship was found between two distribution volumes (DVs) obtained by using 2C and Logan plot. DVs were th
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e highest in the thalamus, moderate in the pons, cerebellum, basal ganglia, lower in cerebral cortices. Good agreement was observed between DV values and results of autoradiographic experiments done in vitro for nAChR density in human brain. The DV during smoking were significantly lower than those under smoke-free state. The PD group showed a tendency for DV reduction in all brain regions and a statistically significant decrease in the brainstem and frontal cortex as compared with the control group. Although age, duration of disease, daily dose of levodopa, duration of PD medication use, and scores on the motor section of Unified Parkinson's Disease Rating Scale were not significantly correlated with DVs in any brain regions, high daily doses of dopamine agonist showed a significant negative correlation with DVs in the stratum, cerebellum, and temporal and parietal cortices.
These findings suggest that patients with PD without dementia can show reductions in brain nAChRs, especially in the brainstem and frontal cortex. They also suggest that dopamine agonists can have a negative influence on the distribution of nAChRs. Our results also indicated that 5IA SPECT may become a useful method for the quantitative measurements for nAChRs in other neurodegenerative disorders. Less
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