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使用高分辨率单光子发射计算机断层扫描对小动物脑多巴胺能神经传递系统进行活体成像。

In vivo imaging of brain dopaminergic neurotransmission system in small animals with high-resolution single photon emission computed tomography.

作者信息

Saji Hideo, Iida Yasuhiko, Kawashima Hidekazu, Ogawa Mikako, Kitamura Youji, Mukai Takahiro, Shimazu Seiichiro, Yoneda Fumiro

机构信息

Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.

出版信息

Anal Sci. 2003 Jan;19(1):67-71. doi: 10.2116/analsci.19.67.

Abstract

High-resolution single photon emission computed tomography (SPECT) provides a unique capability to image the biodistribution of radiolabeled molecules in small laboratory animals. Thus, we applied the high-resolution SPECT to in vivo imaging of the brain dopaminergic neurotransmission system in common marmosets using two radiolabeled ligands, [123I]2beta-carbomethoxy-3beta-(4-iodophenyl)tropane (beta-CIT) as a dopamine transporter (DAT) ligand and [123I]iodobenzamide (IBZM) as a dopamine D2 receptor (D2R) ligand. Specific images of the striatum, a region with a high density of dopaminergic synapses, were obtained at 240 min and 60 min after injection of [123I]beta-CIT and [123I]IBZM, respectively. Furthermore, a significantly low accumulation of [123I]beta-CIT in the striatum was observed in MPTP-treated animals compared with results for a control group, and a similar accumulation in the control group was observed with the pretreatment of deprenyl in the MPTP-treated animals. However, the striatal accumulation of [123I]IBZM showed no changes among the control, MPTP-treated, and deprenyl-MPTP-treated groups. These SPECT imaging results agreed well with those of DA concentration and motor behavior. Since MPTP destroys nigrostriatal dopamine nerves and produces irreversible neurodegeneration associated with Parkinsonian syndrome, SPECT imaging data in this study demonstrated that deprenyl shows its neuroprotective effect on Parkinsonism by protecting against the destruction of presynaptic dopamine neurons.

摘要

高分辨率单光子发射计算机断层扫描(SPECT)具有独特的能力,可对小型实验动物体内放射性标记分子的生物分布进行成像。因此,我们使用两种放射性标记配体,将高分辨率SPECT应用于普通狨猴脑多巴胺能神经传递系统的体内成像,其中[123I]2β-甲氧基羰基-3β-(4-碘苯基)托烷(β-CIT)作为多巴胺转运体(DAT)配体,[123I]碘苯甲酰胺(IBZM)作为多巴胺D2受体(D2R)配体。分别在注射[123I]β-CIT和[123I]IBZM后240分钟和60分钟获得了纹状体(多巴胺能突触高密度区域)的特异性图像。此外,与对照组结果相比,在MPTP处理的动物中观察到纹状体中[123I]β-CIT的积累显著降低,并且在MPTP处理的动物中用司来吉兰预处理后观察到与对照组相似的积累。然而,[123I]IBZM在纹状体中的积累在对照组、MPTP处理组和司来吉兰-MPTP处理组之间没有变化。这些SPECT成像结果与多巴胺浓度和运动行为的结果非常吻合。由于MPTP会破坏黑质纹状体多巴胺神经并产生与帕金森综合征相关的不可逆神经退行性变,本研究中的SPECT成像数据表明,司来吉兰通过保护突触前多巴胺神经元免受破坏而对帕金森病显示出神经保护作用。

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