DEVELOPMENT OF NOVEL RADIOPHARMACEUTICALS FOR EARLY STAGE DIAGNOSIS OF CEREBRAL NEURODEGENERATION.
开发用于脑神经退行性早期诊断的新型放射性药物。
基本信息
- 批准号:14370273
- 负责人:
- 金额:$ 5.12万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B)
- 财政年份:2002
- 资助国家:日本
- 起止时间:2002 至 2004
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
We studied the PET tracer distributions of ligands for dopamine D_1 receptors ([^<11>C]SCH23390) and D_2 receptors ([^<11>C]raclopride) and of the dopamine precursor analog 6-[^<18>F]fluoro-L-3,4-dihydroxyphenylalanine ([^<18>F]FDOPA) in the brain after 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle in rats. The number of methamphetamine-induced rotation was higher at 14 days than that at 3 days following the 6-OHDA lesions. The brains of 6-OHDA treated rats were analyzed by tissue dissection following i.v.bolus of each tracer at 3 days (acute stage) or 3 weeks (chronic stage) postlesion. [^<11>C]Raclopride, but not [^<11>C]SCH23390,showed a higher accumulation in the striatum on the lesion side compared with that on the non-lesioned (intact) side both 3 days and 3 weeks postlesion. On the other hand, a lower accumulation of [^<18>F]FDOPA was found in the striatum on the lesion side 3 days postlesion, and both in the striatum and cerebral cortex on the lesion side 3 … More weeks postlesion. Our studies demonstrate that an increase in [^<11>C]raclopride and a decrease in [^<18>F]FDOPA uptake in the denervated striatum is evident even at 3 days following the 6-OHDA lesions when the degree of methamphetamine-induced rotation is not established. Therefore the combination of a D_2 antagonist and FDOPA may provide a potentially useful method for assessing the effects of dopamine depletion in Parkinson's disease.For SPECT application, radioiodinated derivatives of L-tyrosine, dopamine biosynthesis precursor, were evaluated as diagnosis agents for early detection of neurodegeneration. 3-[^<123>I]iodo-α-methyl-L-tyrosine (I-IMT) and 3-[^<123>I]iodo-α-difluoromethyl-tyrosine methyl ester (I-FTM) were selected as SPECT imaging agents for cerebral amino acid transpoter and dopa decarboxylase (DDC) activity. In the biodistribution study, I-IMT accumulation in the striatum on the lesion side 3 days postlesion increased, then decreased in 2 weeks postlesion, compared with the intact side. On the other hand, I-FTM showed a lower accumulation in the striatum on the lesion side compared with that on the intact side both 3 days and 2 weeks postlesion. It shows that I-FTM, with an affinity to the final enzyme of dopamine biosynthesis, was sensitive for detection of neurodegeneration in acute stage. Thus, both I-IMT and I-FTM may be new candidates of radiopharmaceuticals that can be useful in assessing function of cerebral dopaminergic neuron. Less
我们研究了多巴胺 D_1 受体 ([^<11>C]SCH23390) 和 D_2 受体 ([^<11>C]raclopride) 配体以及多巴胺前体类似物 6-[^<18>F]氟-L-3,4-二羟基苯丙氨酸 ([^<18>F]FDOPA) 在大脑中的 PET 示踪剂分布。 大鼠内侧前脑束的 6-羟基多巴胺 (6-OHDA) 损伤。 6-OHDA 损伤后第 14 天甲基苯丙胺诱导的旋转次数高于第 3 天。在损伤后 3 天(急性期)或 3 周(慢性期)静脉注射每种示踪剂后,通过组织解剖对 6-OHDA 治疗的大鼠的大脑进行分析。在病变后3天和3周,与非病变(完整)侧相比,[^ 11 C]雷氯必利(而非[^ 11 C]SCH23390)在病变侧纹状体中显示出更高的积累。另一方面,在病变后3天的病变侧的纹状体中以及在病变后3周的病变侧的纹状体和大脑皮层中发现[^ 18 F]FDOPA的积累较低。我们的研究表明,去神经纹状体中[^ 11 C]雷氯必利的增加和[^ 18 F]FDOPA摄取的减少即使在6-OHDA损伤后3天(当未确定甲基苯丙胺诱导的旋转程度时)也是明显的。因此,D_2拮抗剂和FDOPA的组合可能提供一种潜在有用的方法来评估多巴胺耗竭对帕金森病的影响。对于SPECT应用,评估了L-酪氨酸(多巴胺生物合成前体)的放射性碘化衍生物作为神经变性早期检测的诊断剂。选择3-[^ 123 I]碘-α-甲基-L-酪氨酸(I-IMT)和3-[^ 123 I]碘-α-二氟甲基-酪氨酸甲酯(I-FTM)作为脑氨基酸转运蛋白和多巴脱羧酶(DDC)活性的SPECT显像剂。在生物分布研究中,与完好侧相比,病变侧纹状体中 I-IMT 的积累在病变后 3 天增加,然后在病变后 2 周减少。另一方面,在病变后 3 天和 2 周,与完好侧相比,I-FTM 在病变侧纹状体中的积累量较低。这表明I-FTM与多巴胺生物合成的最终酶具有亲和力,对急性期神经变性的检测敏感。因此,I-IMT和I-FTM都可能是可用于评估大脑多巴胺能神经元功能的放射性药物的新候选者。较少的
项目成果
期刊论文数量(193)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Regional differences in the expression of Fos-like immunoreactivity after central salt loading in conscious rats : modulation by endogenous vasopressin and role of area postrema
清醒大鼠中枢盐负荷后 Fos 样免疫反应性表达的区域差异:内源性加压素的调节和后区的作用
- DOI:
- 发表时间:2004
- 期刊:
- 影响因子:0
- 作者:柴田真一;他;Chen J;Ishida A;Takeda R;Ishida Y;Nakahara D;Ishida Y;Kato K
- 通讯作者:Kato K
Nagamachi S., Kawai K., et al.: "Serial Change in ^<123>I-MIBG Myocardial Scintigraphy in Non-insulin-dependent Diabetes Mellitus"Ann. Nucl. Med.. 16. 33-38 (2002)
Nagamachi S.、Kawai K.等人:“非胰岛素依赖性糖尿病中^ 123 I-MIBG心肌闪烁显像的系列变化”Ann。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Evaluation of radioiodinated 5-iodo-3(2(S)-azetidinylmethoxy)pyridine as a ligand for SPECT investigation of brain nicotinic acetylcholine receptors.
放射性碘化 5-碘-3(2(S)-氮杂环丁基甲氧基)吡啶作为脑烟碱乙酰胆碱受体 SPECT 研究配体的评价。
- DOI:
- 发表时间:2002
- 期刊:
- 影响因子:0
- 作者:Saji H.;Magata Y.;et al.
- 通讯作者:et al.
Morphological changes in immunopositive cells of ionotropic glutamate receptor subunits during the development of transplanted fetal ventral mesencephalic neurons.
移植胎儿腹侧中脑神经元发育过程中离子型谷氨酸受体亚基免疫阳性细胞的形态变化。
- DOI:
- 发表时间:2002
- 期刊:
- 影响因子:0
- 作者:Ishida Y.;et al.
- 通讯作者:et al.
Effects of metabolite correction for arterial input function on quantitative receptor imaees with ^<11>C-flumazenil in clinical positron emission tomography studies
临床正电子发射断层扫描研究中动脉输入功能代谢物校正对^11C-氟马西尼定量受体图像的影响
- DOI:
- 发表时间:2004
- 期刊:
- 影响因子:0
- 作者:Okazawa H.;Magata Y.;et al.
- 通讯作者:et al.
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
KAWAI Keiichi其他文献
KAWAI Keiichi的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('KAWAI Keiichi', 18)}}的其他基金
Development strategy of tumor diagnostic agent by system upregulated functional biomolecule based on expression analysis of tumor associated transporter
基于肿瘤相关转运蛋白表达分析的系统上调功能生物分子肿瘤诊断剂开发策略
- 批准号:
15K15452 - 财政年份:2015
- 资助金额:
$ 5.12万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Development of a molecular targeted radiolabeled diagnostic agent useful for personalized drug therapy of psychoneurotic diseases
开发可用于精神神经疾病个性化药物治疗的分子靶向放射性标记诊断剂
- 批准号:
25293260 - 财政年份:2013
- 资助金额:
$ 5.12万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
The design strategy for tumor diagnostic agents utilizing the functional biomolecule expression system based on gene expression analysis of tumor cells
基于肿瘤细胞基因表达分析的功能性生物分子表达系统肿瘤诊断剂的设计策略
- 批准号:
24659558 - 财政年份:2012
- 资助金额:
$ 5.12万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
The probe design strategy of post-FDG tumor diagnostic agents based on the functional biomolecule expression analysis of human cultured cells
基于人培养细胞功能生物分子表达分析的FDG后肿瘤诊断剂探针设计策略
- 批准号:
21659286 - 财政年份:2009
- 资助金额:
$ 5.12万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Development of novel radiopharmaceuticals for diagnosis of cerebral neurodegeneration and functional recovery after intrastriatal grafts/gene therapy
开发用于诊断脑神经变性和纹状体移植/基因治疗后功能恢复的新型放射性药物
- 批准号:
20249055 - 财政年份:2008
- 资助金额:
$ 5.12万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Are rare earth elements essential for growth of methylotrophs?
稀土元素对于甲基营养菌的生长至关重要吗?
- 批准号:
20580075 - 财政年份:2008
- 资助金额:
$ 5.12万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Are rare earth elements essential for growth of microorganisms?
稀土元素对微生物的生长至关重要吗?
- 批准号:
17580063 - 财政年份:2005
- 资助金额:
$ 5.12万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
DEVELOPMENT OF NOVEL RADIOPHARMACEUTICALS FOR EARLY STAGE DIAGNOSIS OF CEREBRAL NEURODEGENERATION AND FUNCTIONAL RECOVERRY AFTER INTRASTRIATAL GRAFTS
开发用于脑神经变性早期诊断和纹状移植后功能恢复的新型放射性药物
- 批准号:
17390329 - 财政年份:2005
- 资助金额:
$ 5.12万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
DEVELOPEMENT OF RADIOIODINATED RADIOPHARMACEUTICALS FOR INTERNAL RADIATION THERAPY OF TUMOR BASED ON ITS SPECIFIC METABOLIC ACTIVITY
基于肿瘤特异性代谢活性的用于肿瘤内放射治疗的放射性碘化放射性药物的开发
- 批准号:
12557076 - 财政年份:2000
- 资助金额:
$ 5.12万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
相似海外基金
REAL-WORLD IMPLEMENTATION, DEPLOYMENT AND VALIDATION OF EARLY DETECTION TOOLS AND LIFESTYLE ENHANCEMENT (AD-RIDDLE)
早期检测工具和生活方式增强 (AD-Riddle) 的实际实施、部署和验证
- 批准号:
10106509 - 财政年份:2024
- 资助金额:
$ 5.12万 - 项目类别:
EU-Funded
AD-RIDDLE: Real-World Implementation, Deployment And Validation Of Early Detection Tools And Lifestyle Enhancement
AD-RIDDLE:早期检测工具和生活方式增强的实际实施、部署和验证
- 批准号:
10083470 - 财政年份:2024
- 资助金额:
$ 5.12万 - 项目类别:
EU-Funded
Validating the Use of Point-Of-Care Diagnostics for Early Detection of Human Papillomavirus
验证床旁诊断在人乳头瘤病毒早期检测中的应用
- 批准号:
EP/Y003225/1 - 财政年份:2024
- 资助金额:
$ 5.12万 - 项目类别:
Research Grant
I-Corps: Translation Potential of a Medical Device for Early Detection of Sleep Apnea
I-Corps:医疗设备在早期检测睡眠呼吸暂停方面的转化潜力
- 批准号:
2410765 - 财政年份:2024
- 资助金额:
$ 5.12万 - 项目类别:
Standard Grant
STTR Phase I: Patient-Specific System for Early Detection and Identification of Epileptic Seizures
STTR 第一阶段:早期检测和识别癫痫发作的患者特异性系统
- 批准号:
2322346 - 财政年份:2023
- 资助金额:
$ 5.12万 - 项目类别:
Standard Grant
System development for early detection of infectious disease outbreaks and timely risk assessment
早期发现传染病爆发并及时评估风险的系统开发
- 批准号:
23K09755 - 财政年份:2023
- 资助金额:
$ 5.12万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The early detection of breast cancer using field cacerization.
使用现场癌症化早期检测乳腺癌。
- 批准号:
23K08094 - 财政年份:2023
- 资助金额:
$ 5.12万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Optimizing osteoporosis diagnosis through opportunistic computed tomography: developing an implementation strategy for early detection and intervention.
通过机会性计算机断层扫描优化骨质疏松症诊断:制定早期检测和干预的实施策略。
- 批准号:
484646 - 财政年份:2023
- 资助金额:
$ 5.12万 - 项目类别:
Fellowship Programs
Development of telehome Monitoring-based system that contributes to the prevention and early detection of complications in patients with implantable ventricular assist devices.
开发基于远程监控的系统,有助于预防和及早发现植入式心室辅助装置患者的并发症。
- 批准号:
23K18369 - 财政年份:2023
- 资助金额:
$ 5.12万 - 项目类别:
Grant-in-Aid for Challenging Research (Exploratory)
Developing and testing a novel self-guided digital therapeutic solution for preventing stammering in children: incorporating latest research on early detection and progress evaluation using real-world data
开发和测试一种新颖的自我引导数字治疗解决方案,用于预防儿童口吃:结合使用真实世界数据进行早期检测和进展评估的最新研究
- 批准号:
10072187 - 财政年份:2023
- 资助金额:
$ 5.12万 - 项目类别:
Collaborative R&D