脳シグマ受容体を指標にした加齢・神経変性疾患・脳腫瘍の新しいPET診断法

以大脑西格玛受体为指标的衰老、神经退行性疾病和脑肿瘤的新型 PET 诊断方法

基本信息

批准号：
13557077
负责人：
ISHIWATA Kiichi
金额：
$ 6.78万
依托单位：
Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

项目摘要

We developed [^<11>C]SA4503 as a radioligand for mapping sigma_1 receptors in the central nervous system by positron emission tomography (PET), and successfully visualized the sigma_1 receptors in the human brain at 2000 for the first time. The purposes of the present project are 1)establishment of quantitative measurement of the brain sigma_1 receptors by PET and [^<11>C]SA4503,2)application of the [^<11>C]SA4503 PET to diagnosis of neurological and psychiatric diseases,3)basic studies on the sigma_1 receptors and 4)development of new tracers including radioligands for sigma_2 receptor subtype.We obtained the following findings.1.In general densities of neuroreceptors decrease with aging. However, the binding of radiolabeled SA4503 increased in the rat and monkey brain. The human brain also showed a similar tendency.2.In patients with Alzheimer's disease, the [^<11>C]SA4503 PET detected more sensitively degeneration of the brain than the [^<18>F]FDG PET.3.In patients with Parkinson's disease, the binding of [^<11>C]SA4503 significantly decreased in the affected than the less affected side of the anterior putamen as observed in the [^<11>C]CFT binding.4.Sigma_1 receptor occupancy by haloperidol was evaluated by [^<11>C]SA4503 PET, which would address pharmacological effects of neuroleptics in term of their sigma_1 receptor occupancy.5.The [^<11>C]SA4503 PET may be useful for patients with schizophrenia.6.The [^<11>C]SA4503 PET has potential for tumor diagnosis in the hypogastrium because of low accumulation levels of the activity.7.Brain uptake of [^<11>C]SA4503 was not mediated by P-glycoprotein.8.Several ^<11>C and ^<18>F analogs of [^<11>C]SA4503 were synthesized and evaluated in vivo. Among them we found [^<18>F]FE-SA4503 to be a promising radioligands for tumor diagnosis by PET.

我们通过正电子发射断层扫描（PET）开发了[^<11> c] SA4503作为用于映射中枢神经系统中的Sigma_1受体的放射性物体，并首次成功地可视化了2000年人类大脑中的Sigma_1受体。本项目的目的是1）通过PET和[^<11> c] SA4503,2）在神经和精神疾病的诊断中诊断[^^<11> c] SA4503的应用来建立对脑Sigma_1受体的定量测量亚型。我们获得了以下发现。1。在神经受体的一般密度随着衰老而降低。但是，大鼠和猴子大脑的放射性标记SA4503的结合增加。人类大脑也表现出类似的趋势。2。在阿尔茨海默氏病的患者中，[^<11> c] sa4503 PET比[^<18> f] fdg pet.3.在帕金森氏病的患者中，大脑的敏感性更敏感地变性，比[^<11> c] Sa4503的结合在帕金森氏病中显着降低了。 [^<11> c] Cft结合。4。Sigma_1通过[^<11> c] SA4503 PET评估了氟哌啶醇的受体占用率，这将解决神经疗法在Sigma_1受体占用方面的药理作用。5。5. [^> c] sa4503 PET可能对sapophen.s pets pet the sapoph.11 the 4.^[^35.^[^30]。由于活性的积累水平较低，在低胃中的诊断。7。[ ^<11> c] SA4503的脑吸收未通过p-糖蛋白介导的[ ^<11> C和 ^<11> c] sa4503的[ ^<11> c] sa4503的类似物。其中，我们发现[^<18> f] Fe-SA4503是通过PET诊断肿瘤诊断的有前途的放射线。