INVIVO BINDING OF [C-11] TETRABENAZINE TO VESICULAR MONOAMINE TRANSPORTERS IN MOUSE-BRAIN
INVIVO BINDING OF [C-11] TETRABENAZINE TO VESICULAR MONOAMINE TRANSPORTERS IN MOUSE-BRAIN
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DOI：
10.1016/0024-3205(92)90228-h
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发表时间：
1992-01-01
期刊：
影响因子：
6.1
通讯作者：
KILBOURN, MR
中科院分区：
文献类型：
--
作者：
DASILVA, JN;KILBOURN, MR
静脉注射示踪剂量的[C-11]丁苯那嗪（[C-11]TBZ）后，测定了小鼠脑局部放射性分布的时程。放射性示踪剂摄取到大脑是快速的，与3.2%的注射剂量在大脑中2分钟。从大脑的出口也非常迅速，只有0.21%的注射剂量仍然存在于大脑中60分钟。放射性示踪剂洗脱是最慢的纹状体和下丘脑，与结合到更多的囊泡单胺转运蛋白在这些大脑区域。注射后10分钟放射性配体结合的等级顺序为纹状体>下丘脑>海马>皮质=小脑，与使用囊泡单胺转运蛋白的体外测定所发现的相似。注射后10 min，纹状体/小脑和下丘脑/小脑的最大比值分别为2.85 +/- 0.52和1.69 +/- 0.25。共注射未标记的丁苯那嗪（10 mg/kg）或用利血平预处理（1 mg/kg i. p.，24 h前）用于证明放射性配体在纹状体、下丘脑、皮质、海马和小脑中的特异性结合。[C-11]TBZ的分布不受神经元多巴胺摄取抑制剂GBR 12935（20 mg/kg i. p.，30分钟前）。因此，[C-11]四苯那嗪是一种很有前途的新放射性配体，可用于使用正电子发射断层扫描法进行单胺能神经元的体内研究。
The time course of regional mouse brain distribution of radioactivity after i.v. injection of a tracer dose of [C-11]tetrabenazine ([C-11]TBZ) has been determined. Radiotracer uptake into brain is rapid, with 3.2% injected dose in the brain at 2 min. Egress from the brain is also very rapid, with only 0.21% of the injected dose still present in brain at 60 min. Radiotracer washout is slowest from the striatum and hypothalamus, consistent with binding to the higher numbers of vesicular monoamine transporters in those brain regions. The rank order of radioligand binding at 10 min after injection is striatum > hypothalamus > hippocampus > cortex = cerebellum, similar to that found using in vitro assays of the vesicular monoamine transporters. Maximum ratios of striatum/cerebellum and hypothalamus/cerebellum were 2.85 +/- 0.52 and 1.69 +/- 0.25, respectively, at 10 min after injection. Co-injection of unlabeled tetrabenazine (10 mg/kg) or pretreatment with reserpine (1 mg/kg i.p., 24 h prior) was used to demonstrate specific binding of radioligand in striatum, hypothalamus, cortex, hippocampus and cerebellum. Distribution of [C-11]TBZ was unaffected by pretreatment with the neuronal dopamine uptake inhibitor GBR 12935 (20 mg/kg i.p., 30 min prior). [C-11]Tetrabenazine is thus a promising new radioligand for the in vivo study of monoaminergic neurons using Positron Emission Tomography.