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

基本信息

  • 批准号:
    17390329
  • 负责人:
  • 金额:
    $ 7.69万
  • 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:
    2005
  • 资助国家:
    日本
  • 起止时间:
    2005 至 2007
  • 项目状态:
    已结题

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 ([^<18>F]FDOPA) after 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle in rats. The brains of 6-OHDA treated rats were analyzed by tissue dissection 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 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 weeks postlesion. An increase in raclopride and a decrease in FDOPA uptake in the denervated striatum is evident even at 3 days following the 6-OHDA lesions when the degree of methamphetamine (MAP)-induced rotation is not esta … More blished. Therefore the combination of D_2 antagonist and FDOPA may provide a potentially useful method for assessing the effects of dopamine depletion in Parkinson's disease.In addition, we examined the topological specificity of MAP-induced activation of the immediate-early gene proteins, Fos and Zif268, in the nigrostriatal system in a unilateral 6-OHDA rat model of Parkinson's disease with or without intrastriatal grafts of fetal ventral mesencephalon. The differential expression of Fos and Zif268 was observed among the three regions of the nigrostriatal system following MAP in the 6-OHDA rats. This may suggest that Fos and Zif268 therefore possess gene-specific and region-specific functions in the basal ganglia nuclei.For SPECT application, radioiodinated derivatives of dopamine biosynthesis precursor, [^<123>I]I-IMT and [^<123>I]I-FTM, were evaluated as diagnosis agents for early detection of neurodegeneration. 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. 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 sensitive radiopharmaceuticals in detecting function of cerebral dopaminergic neuron. Less
我们研究了6-羟基多巴胺(6-OHDA)损毁大鼠内侧前脑束后,多巴胺D_1受体([^<11>C] SCH 23390)和D_2受体([^<11>C]雷氯必利)配体以及多巴胺前体类似物([^<18>F]FDOPA)的PET示踪分布。在损伤后3天(急性期)或3周(慢性期)通过组织解剖分析6-OHDA处理的大鼠的脑。[^<11>C] Raclopride,而不是[^<11>C] SCH 23390,在损伤侧的纹状体中的蓄积高于损伤后3天和3周的完整侧。另一方面,<18>损伤后3天在损伤侧的纹状体中发现较低的[^ F]FDOPA积累,并且损伤后3周在损伤侧的纹状体和大脑皮层中均发现较低的[^ F]FDOPA积累。即使在6-OHDA损伤后3天,当甲基苯丙胺(MAP)诱导的旋转程度不确定时,去神经纹状体中雷氯必利的增加和FDOPA摄取的减少也是明显的。 ...更多信息 幸福此外,我们还研究了MAP诱导的即刻早期基因蛋白Fos和Zif 268激活的拓扑学特异性。在单侧6-OHDA帕金森病大鼠模型的黑质纹状体系统中,有或没有胎儿腹侧中脑的纹状体内移植物。6-OHDA大鼠MAP后黑质纹状体系统3个区域Fos和Zif 268的表达存在差异。因此,Fos和Zif 268在基底节细胞核中具有基因特异性和区域特异性功能。在SPECT应用中,放射性碘标记的多巴胺生物合成前体衍生物[^<123>I]I-IMT和[^<123>I]I-FTM可作为神经退行性变的早期诊断剂。在生物分布研究中,与完整侧相比,损伤侧纹状体中的I-IMT在损伤后3天增加,然后在损伤后2周减少。另一方面,I-FTM在损伤侧纹状体中的蓄积量低于损伤侧,损伤后3天和2周均如此。I-FTM对多巴胺生物合成的最终酶具有亲和力,对急性期神经退行性变的检测敏感。因此,I-IMT和I-FTM可能是检测脑多巴胺能神经元功能的敏感放射性药物的新候选者。少

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
The structural and pharmacokinetic properties of oxidized human serum albumin, advanced oxidation protein products (AOPP)
  • DOI:
    10.2133/dmpk.21.140
  • 发表时间:
    2006-01-01
  • 期刊:
  • 影响因子:
    2.1
  • 作者:
    Iwao, Yasunori;Anraku, Makoto;Otagiri, Masaki
  • 通讯作者:
    Otagiri, Masaki
Diagnosis of misery perfusion using noninvasive ^<15>O gas PET.
使用无创15 O气体PET诊断灌注痛苦。
  • DOI:
  • 发表时间:
    2006
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Kobayashi M.;Okazawa H.;Kawai K.;et al.
  • 通讯作者:
    et al.
Peripheral ghrelin transmits orexigenic signals through the noradrenergic pathway from the hindbrain to the hypothalamus
  • DOI:
    10.1016/j.cmet.2006.09.004
  • 发表时间:
    2006-10-01
  • 期刊:
  • 影响因子:
    29
  • 作者:
    Date, Yukari;Shimbara, Takuya;Nakazato, Masamitsu
  • 通讯作者:
    Nakazato, Masamitsu
放射化学と放射線化学三訂版
放射化学与辐射化学第三版
  • DOI:
  • 发表时间:
    2006
  • 期刊:
  • 影响因子:
    0
  • 作者:
    河村正一;井上修;荒野泰;川井恵一
  • 通讯作者:
    川井恵一
Elevation of 3-[^<125>I]iodo-α-methyl-L-tyrosine tissue accumulation by regulation of renal excretion with OAT inhibitors.
通过用OAT抑制剂调节肾排泄来升高3-[^ 125 I]碘-α-甲基-L-酪氨酸组织积累。
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KAWAI Keiichi其他文献

KAWAI Keiichi的其他文献

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{{ 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:
    $ 7.69万
  • 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:
    $ 7.69万
  • 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:
    $ 7.69万
  • 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:
    $ 7.69万
  • 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:
    $ 7.69万
  • 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:
    $ 7.69万
  • 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:
    $ 7.69万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Effects of rare earth elements on living matter
稀土元素对生物体的影响
  • 批准号:
    20900118
  • 财政年份:
    2004
  • 资助金额:
    $ 7.69万
  • 项目类别:
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。
  • 批准号:
    14370273
  • 财政年份:
    2002
  • 资助金额:
    $ 7.69万
  • 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:
    $ 7.69万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)

相似海外基金

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:
    $ 7.69万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
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