在帕金森病大鼠模型中进行 SERT 选择性[18F]FPBM 和 VMAT2 选择性[18F]AV-133 放射性示踪剂的体内研究。
In vivo studies of the SERT-selective [18F]FPBM and VMAT2-selective [18F]AV-133 radiotracers in a rat model of Parkinson's disease.
机构信息
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
出版信息
Nucl Med Biol. 2010 May;37(4):479-86. doi: 10.1016/j.nucmedbio.2010.01.006.
INTRODUCTION
The utility of [(18)F]FPBM [2-(2'-((dimethylamino)methyl)-4'-(3-[(18)F]-fluoropropoxy)phenylthio)benzenamine], a selective serotonin transporter (SERT) tracer, and [(18)F]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.
METHODS
Positron emission tomography (PET) imaging of three 6-OHDA unilateral lesioned male Sprague Dawley rats (Rats 1-3) were performed with [(18)F]FPBM and [(18)F]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 [(18)F]FPBM and the dopamine transporter ligand, [(125)I]IPT [N-(3'-[(125)I]-iodopropen-2'-yl)-2-beta-carbomethoxy-3-beta-(4-chloro phenyl) tropane, for confirmation. Biodistribution of [(18)F]FPBM in a separate group of p-chloroamphetamine (PCA) treated rats were also performed.
RESULTS
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 (p-chloroamphetamine) showed a significant reduction of [(18)F]FPBM uptake in the cortex and hypothalamus regions of the brain.
CONCLUSION
The preliminary data suggest that [(18)F]FPBM and [(18)F]AV-133 may be useful for the examination of serotonergic and dopaminergic neuron integrity, respectively, in the living brain.
介绍
[(18)F]FPBM [2-(2'-((二甲氨基)甲基)-4'-(3-[(18)F]-氟丙氧基)苯基硫代)苯甲胺]，一种选择性血清素转运体（SERT）示踪剂，和[(18)F]AV-133 [（+）-2-羟基-3-异丁基-9-（3-氟丙氧基）-10-甲氧基-1,2,3,4,6,7-六氢-11bH-苯并[a]喹啉]，一种选择性囊泡单胺转运体 2（VMAT2）示踪剂，在 6-羟多巴胺（6-OHDA）单侧损伤大鼠模型中进行了测试。
方法
对 3 只 6-OHDA 单侧损伤的雄性 Sprague Dawley 大鼠（大鼠 1-3）进行正电子发射断层扫描（PET）成像，用 [(18)F]FPBM 和 [(18)F]AV-133 分别检测 SERT 和 VMAT2 结合的变化，然后取出大鼠的大脑进行体外放射自显影分析，用 [(125)I]IPT [N-(3'-[(125)I]-碘丙烯-2'-基)-2-β-羧甲氧基-3-β-(4-氯苯基)托烷]，确认多巴胺转运体配体。还对一组单独接受 p-氯苯丙胺（PCA）处理的大鼠进行了 [(18)F]FPBM 的生物分布研究。
结果
PET 图像分析显示，与右侧（未损伤侧）纹状体相比，左纹状体的 SERT 结合减少程度不同（大鼠 1=-11%，大鼠 2=-4%，大鼠 3=-43%；n=2），VMAT2 结合明显缺失（大鼠 1=-87%，大鼠 2=-72%，大鼠 3=-91%；n=1）。PET 成像结果与定量体外放射自显影结果相符。用选择性血清素毒素（p-氯苯丙胺）处理的大鼠，大脑皮层和下丘脑区域的 [(18)F]FPBM 摄取明显减少。
结论
初步数据表明，[(18)F]FPBM 和 [(18)F]AV-133 可能分别用于检测活体大脑中 5-羟色胺能和多巴胺能神经元的完整性。
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