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

放射性碘标记的 (-)-o-碘维沙考可用于诊断阿尔茨海默病。

• 批准号: 11670878
• 负责人: SHIBA Kazuhiro
• 金额: $ 2.18万
• 依托单位: KANAZAWA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670878/
• 关键词: Iodovesamicol; Cholinergic neurons; Acetylcholine Transporter; Alzheimer's Disease

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.

我们评价了放射性碘标记的(-)-邻碘-阿米考[(-)-OIV]作为一种选择性囊泡性乙酰胆碱转运体(VAChT)标记剂的潜力。在体外实验中，(-)-对映体[(-)-邻碘对映体((-)-OIV)，(-)-间碘对映体((-)-MIV)，(-)-维沙米考]比(+)-对映体[(+)-OIV，(+)MLV，(+)-维沙米考]对VAChht有更高的亲和力。(-)-OIV和(-)-MLV对Vacht的亲和力与(-)-维沙米考相同。对Sigma受体(σ-1、σ-2)，(-)-OIV(Ki=62.2nM(对σ-1)和554nM(对σ-2))的亲和力低于(-)-MLV(Ki=4.5nM(对σ-1)和42.9nM(对σ-2))。在体脑区域分布研究和体外放射自显影研究表明，(-)-[~(125)]O_(IV)在大鼠脑内的蓄积特征与[~3H]维沙米考非常相似。体内置换研究表明，(-)[^&lt；125&gt；I]OIV与Vacht的结合亲和力很高，与Sigma受体的结合亲和力很低。此外，在单侧NBM损毁大鼠，(-)-[125；gt；I]OIV积聚的减少率(17%)显著高于(-)[-][125mIV]MIV(10%)(P&lt；0.01)。这些结果表明，(-)-OIV是一种比(-)MLV更好的选择性囊泡乙酰胆碱转运体标记剂。放射性碘(-)-OIV可能对阿尔茨海默病的诊断有潜在的帮助。

项目成果

Ikeda, E.: "Raduction of vesicular acetylcholine transporter in B-amyloid protein infused rats with memory impairment"Nuclear Medicine Communications. 21. 933-937 (2000)

Ikeda, E.：“记忆障碍 B-淀粉样蛋白注入大鼠中囊泡乙酰胆碱转运蛋白的减少”核医学通讯。

Shiba, K.: "The potential of radioiodinated (-)-m-iodovesamicol for diagnosing cholinergic deficit dementia"Nuclear. Medicine and Biology. 28. 261-264 (2001)

Shiba, K.：“放射性碘化 (-)-m-iodovesamicol 诊断胆碱能缺陷性痴呆的潜力”核。

Ikeda, E.: "Reduction of vesicular acetylcholine transporter in β-amyloid protein infused rats with memory impairment"Nuclear Medicine Communication. 21. 933-937 (2000)

Ikeda, E.：“记忆障碍的 β-淀粉样蛋白注入大鼠中囊泡乙酰胆碱转运蛋白的减少”核医学通讯 21. 933-937 (2000)。

Ikeda, E.: "Effect of vagal autotransplantation on quantitative [3H]-vesamicol binding image in rats with unilateral lesions of nucleus basalis magnocellularis"NeuroReport. 300. 33-36 (2001)

Ikeda, E.：“迷走神经自体移植对大细胞基底核单侧损伤大鼠定量 [3H]-vesamicol 结合图像的影响”NeuroReport。

E.Ikeda,K.Shiba,: "Reduction of vesicular acetylcholine transporter in β-amyloid protein infused rats with memory impairment."Nucl.Med.Commun.. 21. 933-937 (2000)

E.Ikeda, K.Shiba,：“β-淀粉样蛋白输注大鼠记忆障碍中囊泡乙酰胆碱转运蛋白的减少。”Nucl.Med.Commun.. 21. 933-937 (2000)