In vivo PET measurement of expression of dopamine D2 receptor gene injected into rat striatum

体内PET测量大鼠纹状体注射多巴胺D2受体基因的表达

基本信息

批准号：
10558115
负责人：
ISHIWATA Kiichi
金额：
$ 8.45万
依托单位：
TOKYO METROPOLITAN INSTITUTE OF GERONTOLOGY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

As the basic study of gene therapy, we investigated whether the expression of dopamine DィイD22ィエD2 receptor (DィイD22ィエD2R) gene injected into the rat striatum was evaluated in vivo by positron emission tomography (PET). preliminarily we established that the striatal DィイD22ィエD2R was evaluated by PET with ィイD111ィエD1C-labeled DィイD22ィエD2R-specific ligands by using normal rats and a rat model for striatal neurodegenerative diseases induced by striatal injection of quinolinic acid. To overcome the spatial resolution of PET camera, a technique of PET-MRI registration on the rat brain was developed.PET measurement demonstrated that the uptake of three kinds of DィイD22ィエD2R-specific ligands, [ィイD111ィエD1C]raclopride, [ィイD111ィエD1C]nemonapride and [ィイD111ィエD1C]N-methylspiperone was higher in the striatum injected with the vectors for DィイD22ィエD2R than the contralateral striatum injected with a control vector 2-3 days after injection. The uptake of [ィイD111ィエD1C]SCH 23390, a dopamine DィイD21ィエD2 receptor … More specific ligand, or [ィイD111ィエD1C]β-CIT-FP, a dopamine transporter specific tracer, was not different between bilateral striata, and co-injection of excess unlabeled raclopride inhibited the uptake of [ィイD111ィエD1C]raclopride, suggesting the PET signal reflects the DィイD22ィエD2R-specific gene-expression. These findings were confirmed by ex vivo and in vitro autoradiography. At day 16 the increased uptake of [ィイD111ィエD1C]raclopride declined to basal level, suggesting that the gene expression is temporary.We concluded that PET imaging is capable of detecting adenovirus-mediated gene transfer in vivo. This technique represents a major advance over in vitro ARG analysis of DィイD22ィエD2R binding which must be done post-hoc. PET imaging permits in vivo analysis of the efficiency of DィイD22ィエD2R gene transfer that can be followed longitudinally and related to any functional changes being observed. Such imaging will prove highly valuable for assessment of gene transfer using this and similar vectors. Less

作为基因疗法的基本研究，我们研究了通过阳性发射断层扫描（PET）评估了注入大鼠纹状体中多巴胺D22E D2受体（D22E D2R）基因的表达。我们首先确定，通过使用正常大鼠使用D111E标记的D1C标记的D22E D22E D22E D22E D22E D2R进行评估，该配体使用正常大鼠和大鼠模型用于纹状体神经退行性疾病。 To overcome the spatial resolution of PET camera, a technique of PET-MRI registration on the rat brain was developed.PET measurement demonstrated that the uptake of three kinds of D22R-specific ligands, [D111 D1C]raclopride, [D111 D1C]nemonapride and [D111 D1C]N-methylspiperone was higher in the striatum injection with the vectors for注射后2-3天，D22D2R比对对纹状体注射的对侧纹状体注射。 The uptake of [II D111 D1C]SCH 23390, a dopamine D21 D2 receptor … More specific ligand, or [II D111 D1C]β-CIT-FP, a dopamine transporter specific tracer, was not different between bilateral striata, and co-injection of excess unlabeled raclopride inhibited the uptake of [II D111 D1C]raclopride,提示宠物信号反映了D22E D2R特异性基因表达。这些发现通过体内和体外放射自显影证实。在第16天，[D111E D1C] RACLOPRIDE的摄取量增加到基本水平，表明该基因表达是暂时的。我们得出的结论是，PET成像能够检测体内腺病毒介导的基因转移。该技术代表了对D22E D2R结合的体外ARG分析的重大进展，该分析必须在事后进行。 PET成像允许在体内分析D22E D2R基因转移的效率，该效率可以纵向遵循，并且与观察到的任何功能变化有关。这种成像将证明对于使用此矢量和类似矢量评估基因转移非常有价值。较少的