Confirmation of fenfluramine effect on 5-HT1B receptor binding of [11C]AZ10419369 using an equilibrium approach
Confirmation of fenfluramine effect on 5-HT1B receptor binding of [11C]AZ10419369 using an equilibrium approach
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DOI：
10.1038/jcbfm.2011.172
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发表时间：
2012-04-01
影响因子：
6.3
通讯作者：
Farde, Lars
中科院分区：
文献类型：
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作者：
Finnema, Sjoerd J.;Varrone, Andrea;Farde, Lars
用正电子发射断层扫描(PET)评估活体大脑中5-羟色胺的释放可能因缺乏合适的放射性配体而受到阻碍。我们以前报道过芬氟拉明在猴子体内引起剂量依赖性的特异性结合减少，使用经典的置换范例与[C-11]AZ10419369推注。这项研究的目的是用猴子的平衡方法来证实我们之前的发现。使用[C-11]AZ10419369团注方案，在三只食蟹猴身上进行了总共24次PET测量。进行初步的正电子发射计算机断层扫描测量，以评估合适的K-BOL值。芬氟拉明对[C-11]AZ10419369结合的影响在置换和预处理范式中进行了评估。芬氟拉明对[C-11]AZ10419369结合电位(BPND)的影响在置换范式中呈剂量依赖性，在预处理范式中得到证实。芬氟拉明(5.0 mg/kg)给药后，枕叶皮质BPND由1.38+/-0.04降至0.84+/-0.09，下降了39%。本研究证实新的5-HT1B受体放射性配基[C-11]AZ10419369对芬氟拉明引起的体内内源性5-羟色胺水平的变化敏感。更先进的方法适用于探索用[C-11]AZ10419369和PET测量的5-羟色胺释放的灵敏度极限。《脑血流与代谢杂志》(2012年)32685-695；doi：10.1038/jcbfm.2011.172；2011年12月14日在线发布
Assessment of serotonin release in the living brain with positron emission tomography (PET) may have been hampered by the lack of suitable radioligands. We previously reported that fenfluramine caused a dose-dependent reduction in specific binding in monkeys using a classical displacement paradigm with bolus administration of [C-11]AZ10419369. The aim of this study was to confirm our previous findings using an equilibrium approach in monkey. A total of 24 PET measurements were conducted using a bolus infusion protocol of [C-11]AZ10419369 in three cynomolgus monkeys. Initial PET measurements were performed to assess suitable K-bol values. The fenfluramine effect on [C-11]AZ10419369 binding was evaluated in a displacement and pretreatment paradigm. The effect of fenfluramine on [C-11]AZ10419369 binding potential (BPND) was dose-dependent in the displacement paradigm and confirmed in the pretreatment paradigm. After pretreatment administration of fenfluramine (5.0 mg/kg), the mean BPND of the occipital cortex decreased by 39%, from 1.38 +/- 0.04 to 0.84 +/- 0.09. This study confirms that the new 5-HT1B receptor radioligand [C-11]AZ10419369 is sensitive to fenfluramine-induced changes in endogenous serotonin levels in vivo. The more advanced methodology is suitable for exploring the sensitivity limit to serotonin release as measured using [C-11]AZ10419369 and PET. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 685-695; doi:10.1038/jcbfm.2011.172; published online 14 December 2011