Use of [18F]FDOPA-PET for in vivo evaluation of dopaminergic dysfunction in unilaterally 6-OHDA-lesioned rats.
Use of [18F]FDOPA-PET for in vivo evaluation of dopaminergic dysfunction in unilaterally 6-OHDA-lesioned rats.
复制标题
DOI：
10.1186/2191-219x-1-25
复制
发表时间：
2011-11-10
期刊：
影响因子：
3.2
通讯作者：
Watanabe Y
中科院分区：
文献类型：
--
作者：
Kyono K;Takashima T;Katayama Y;Kawasaki T;Zochi R;Gouda M;Kuwahara Y;Takahashi K;Wada Y;Onoe H;Watanabe Y
我们评估了l -3,4-二羟基-6-[18F]氟苯丙氨酸（[18F]FDOPA）正电子发射断层扫描（PET）作为评估单侧6-羟基多巴胺（6-OHDA）损伤大鼠多巴胺能功能障碍严重程度的方法，将其与定量生化、免疫组织化学和行为测量进行比较。将不同剂量（0、7、14、28 μg）的6-OHDA单侧注射至雄性sd大鼠右侧纹状体。通过[18F]FDOPA-PET、纹状体多巴胺（DA）和DA代谢物水平测定、酪氨酸羟化酶（TH）免疫染色和甲基苯丙胺诱导旋转试验评估纹状体多巴胺能功能活性。用芳香l-氨基酸脱羧酶和儿茶酚o -甲基转移酶（COMT）抑制剂预处理大鼠，观察双侧纹状体中[18F]FDOPA的积累。单侧胃内注射6-OHDA可显著降低[18F]FDOPA积累的部位特异性。[18F]FDOPA在同侧纹状体积累的拓扑分布模式与th染色相应切片的模式吻合较好。Patlak图Ki值与纹状体DA及其代谢物水平呈显著正相关（r = 0.958）。Ki值（r = -0.639）与DA及其代谢物水平（r = -0.719）与甲基苯丙胺诱导的旋转次数呈显著负相关。用[18F]FDOPA-PET测定Ki值与多巴胺能功能障碍的严重程度显著相关。[18F]FDOPA-PET使得对6- ohda损伤大鼠多巴胺能功能进行纵向评价成为可能，这对帕金森病（PD）新药和治疗方法的开发具有重要意义。
We evaluated the utility of L-3,4-dihydroxy-6-[18F]fluoro-phenylalanine ([18F]FDOPA) positron emission tomography (PET) as a method for assessing the severity of dopaminergic dysfunction in unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats by comparing it with quantitative biochemical, immunohistochemical, and behavioral measurements. Different doses of 6-OHDA (0, 7, 14, and 28 μg) were unilaterally injected into the right striatum of male Sprague-Dawley rats. Dopaminergic functional activity in the striatum was assessed by [18F]FDOPA-PET, measurement of striatal dopamine (DA) and DA metabolite levels, tyrosine hydroxylase (TH) immunostaining, and methamphetamine-induced rotational testing. Accumulation of [18F]FDOPA in the bilateral striatum was observed in rats pretreated with both aromatic L-amino acid decarboxylase and catechol-O-methyltransferase (COMT) inhibitors. Unilateral intrastriatal injection of 6-OHDA produced a significant site-specific reduction in [18F]FDOPA accumulation. The topological distribution pattern of [18F]FDOPA accumulation in the ipsilateral striatum agreed well with the pattern in TH-stained corresponding sections. A significant positive relationship was found between Patlak plot Ki values and striatal levels of DA and its metabolites (r = 0.958). A significant negative correlation was found between both Ki values (r = -0.639) and levels of DA and its metabolites (r = -0.719) and the number of methamphetamine-induced rotations. Ki values determined using [18F]FDOPA-PET correlated significantly with the severity of dopaminergic dysfunction. [18F]FDOPA-PET makes it possible to perform longitudinal evaluation of dopaminergic function in 6-OHDA-lesioned rats, which is useful in the development of new drugs and therapies for Parkinson's disease (PD).