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采用[11C]PE2I进行体内正电子发射断层扫描(PET)测量,以评估将胎儿中脑移植到单侧6-羟基多巴胺(6-OHDA)损伤大鼠体内的情况。

In vivo PET measurements with [11C]PE2I to evaluate fetal mesencephalic transplantations to unilateral 6-OHDA-lesioned rats.

作者信息

Inaji Motoki, Yoshizaki Takahito, Okauchi Takashi, Maeda Jun, Nagai Yuji, Nariai Tadashi, Ohno Kikuo, Ando Kiyoshi, Okano Hideyuki, Obayashi Shigeru, Suhara Tetsuya

机构信息

Brain Imaging Project, National Institute of Radiological Science, Inage-ku, Chiba, Japan.

出版信息

Cell Transplant. 2005;14(9):655-63. doi: 10.3727/000000005783982684.

Abstract

Positron emission tomography (PET) is a useful tool to assess and visualize neurotransmissions in vivo. In this study, we performed repeated PET scans with [11C]PE2I, a tracer of the dopamine transporter, to evaluate the alteration of the expression of dopamine (DA) transmission component after a fetal mesencephalic transplantation. The fetal mesencephalic cells were transplanted into the striatum of unilateral 6-OHDA-lesioned rats. PET scans with [11C]PE2I were performed to evaluate the DA transporter before and 2 and 4 weeks after the transplantation. Rotation behavior tests, in vitro autoradiography, measurements of DA contents in the striatum by high-performance liquid chromatography (HPLC), and tyrosine hydroxylase (TH) immunohistological examinations were performed at the same time points and examined for their relationship to changes in the dopamine transporter. The number of ipsilateral rotations induced by methamphetamine injections decreased. DA contents in the striatum measured with HPLC significantly increased. In the PET study, the binding potential of [11C]PE2I increased at 4 weeks. The results of the in vitro autoradiography study corresponded with those of the PET study. The degrees of the change in the binding potentials correlated with those of the numbers of rotations in the behavioral study and the DA contents in the striatum. In the histological examination, TH-positive cells with axons were observed at 2 and 4 weeks after the transplantation. As the dopamine transporter exists only in the axon terminal of DA neurons, these results suggested that PET measurements of [11C]PE2I binding indicated not only survival, but maturity and functioning of the transplanted cells. Repeated PET measurements of DA transporters are a useful tool in assessing the effectiveness of neural transplantations.

摘要

正电子发射断层扫描(PET)是一种在体内评估和可视化神经传递的有用工具。在本研究中,我们使用多巴胺转运体示踪剂[11C]PE2I进行了重复PET扫描,以评估胎儿中脑移植后多巴胺(DA)传递成分表达的变化。将胎儿中脑细胞移植到单侧6-OHDA损伤大鼠的纹状体中。在移植前以及移植后2周和4周进行[11C]PE2I PET扫描,以评估DA转运体。在相同时间点进行旋转行为测试、体外放射自显影、用高效液相色谱(HPLC)测量纹状体中的DA含量以及酪氨酸羟化酶(TH)免疫组织学检查,并检查它们与多巴胺转运体变化的关系。甲基苯丙胺注射诱导的同侧旋转次数减少。用HPLC测量的纹状体中DA含量显著增加。在PET研究中,[11C]PE2I的结合潜力在4周时增加。体外放射自显影研究的结果与PET研究的结果一致。结合潜力的变化程度与行为研究中的旋转次数以及纹状体中的DA含量的变化程度相关。在组织学检查中,在移植后2周和4周观察到有轴突的TH阳性细胞。由于多巴胺转运体仅存在于DA神经元的轴突末端,这些结果表明,[11C]PE2I结合的PET测量不仅表明移植细胞的存活,还表明其成熟度和功能。重复进行DA转运体的PET测量是评估神经移植有效性的有用工具。

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