In vivo studies of the SERT-selective [18F]FPBM and VMAT2-selective [18F]AV-133 radiotracers in a rat model of Parkinson's disease.
In vivo studies of the SERT-selective [18F]FPBM and VMAT2-selective [18F]AV-133 radiotracers in a rat model of Parkinson's disease.
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DOI：
10.1016/j.nucmedbio.2010.01.006
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发表时间：
2010-05
影响因子：
3.1
通讯作者：
Kung HF
中科院分区：
文献类型：
--
作者：
Wang JL;Oya S;Parhi AK;Lieberman BP;Ploessl K;Hou C;Kung HF
[18F]FPBM的效用（2-（2′-（（二甲氨基）甲基）-4′-（3-[18F]-氟丙氧基）苯硫基）苯胺），选择性5-羟色胺转运蛋白（SERT）示踪剂，和[18F]AV-133（（+）-2-羟基-3-异丁基-9-甲基-N-（2-（2-（3-[18F]-氟丙氧基）苯硫基）苯胺），（3-氟丙氧基）-10-甲氧基-1，2，3，4，6，7-六氢-11bH-苯并[a]喹嗪），选择性囊泡单胺转运蛋白2（VMAT 2）示踪剂，在6-羟基多巴胺（6-OHDA）单侧损伤大鼠模型中测试。用[18 F]FPBM和[18 F]AV-133对三只6-OHDA单侧损伤的雄性Sprague道利大鼠（大鼠#1-3）进行PET成像，以检查是否可以在脑中分别检测到SERT和VMAT 2结合的变化。然后取出三只大鼠的大脑，用[18 F]FPBM和多巴胺转运蛋白配体[125 I]IPT通过体外放射自显影进行检查以进行确认。PET图像分析显示不同水平的SERT结合减少（大鼠#1 =-11%，大鼠#2 =-4%，大鼠#3 =-43%; n = 2）以及VMAT 2结合的明确和确定的丧失（大鼠#1 = − 87%，大鼠#2 = − 72%，大鼠#3 = −91%; n = 1）与右侧（非损伤侧）纹状体相比。PET成像的结果与定量体外放射自显影相证实。用选择性5-羟色胺毒素（PCA，对氯苯丙胺）处理的大鼠显示大脑皮层和下丘脑区域的摄取显著减少。初步数据表明，[18 F]FPBM和[18 F]AV-133分别可用于检查活体脑中多巴胺能和多巴胺能神经元的完整性。
The utility of [18F]FPBM (2-(2′-((dimethylamino)methyl)-4′-(3-[18F]-fluoropropoxy)phenylthio)benzenamine), a selective serotonin transporter (SERT) tracer, and [18F]AV-133 ((+)-2-Hydroxy-3-isobutyl-9-(3-fluoropropoxy)-10-methoxy-1,2,3,4,6,7-hexahydro-11bH-benzo[a]quinolizine), a selective vesicular monoamine transporter 2 (VMAT2) tracer, were tested in the 6-hydroxydopamine (6-OHDA) unilateral lesioned rat model. PET imaging of three 6-OHDA unilateral lesioned male Sprague Dawley rats (rats #1-3) were performed with [18F]FPBM and [18F]AV-133 to examine whether changes in SERT and VMAT2 binding, respectively, could be detected in the brain. The brains of the three rats were then removed and examined by in vitro autoradiography with [18F]FPBM and the dopamine transporter ligand, [125I]IPT, for confirmation. PET image analysis showed varying levels of SERT binding reduction (rat #1 = −11%, rat #2 = −4%, rat #3 = −43%; n = 2) and a clear and definitive loss of VMAT2 binding (rat #1 = −87%, rat #2 = −72%, and rat #3 = −91%; n = 1) in the left striatum when compared to the right (non-lesioned side) striatum. The results from PET imaging were corroborated with quantitative in vitro autoradiography. Rats treated with a selective serotonin toxin (PCA, p-chloroamphetamine) showed a significant reduction of uptake in the cortex and hypothalamus regions of the brain. The preliminary data suggest that [18F]FPBM and [18F]AV-133 may be useful for the examination of serotonergic and dopaminergic neuron integrity, respectively, in the living brain.
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影响因子：
1.6
作者：
Huang, Ya-Yao;Huang, Wen-Sheng;Shiue, Chyng-Yann
通讯作者：
Shiue, Chyng-Yann
影响因子：
7.3
作者：
Jarkas, Nachwa;Voll, Ronald J.;Goodman, Mark M.
通讯作者：
Goodman, Mark M.
影响因子：
4.7
作者：
Garg, Sudha;Thopate, Shankar R.;Garg, Pradeep K.
通讯作者：
Garg, Pradeep K.
影响因子：
3.8
作者：
LUTHMAN, J;BOLIOLI, B;JONSSON, G
通讯作者：
JONSSON, G
影响因子：
7.3
作者：
Plisson, Christophe;Stehouwcr, Jeffrey S.;Goodman, Mark M.
通讯作者：
Goodman, Mark M.