Phan Jenny-Ann, Landau Anne M, Wong Dean F, Jakobsen Steen, Nahimi Adjmal, Doudet Doris J, Gjedde Albert
1] Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark [2] Department of Biomedicine, Aarhus University, Aarhus, Denmark.
1] Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark [2] Center of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark.
J Cereb Blood Flow Metab. 2015 Mar;35(3):501-11. doi: 10.1038/jcbfm.2014.225. Epub 2015 Jan 7.
We quantified the binding potentials (BPND) of [(11)C]yohimbine binding in rat brain to alpha-2 adrenoceptors to evaluate [(11)C]yohimbine as an in vivo marker of noradrenergic neurotransmission and to examine its sensitivity to the level of noradrenaline. Dual [(11)C]yohimbine dynamic positron emission tomography (PET) recordings were applied to five Sprague Dawley rats at baseline, followed by acute amphetamine administration (2 mg/kg) to induce elevation of the endogenous level of noradrenaline. The volume of distribution (VT) of [(11)C]yohimbine was obtained using Logan plot with arterial plasma input. Because alpha-2 adrenoceptors are distributed throughout the brain, the estimation of the BPND is complicated by the absence of an anatomic region of no displaceable binding. We used the Inhibition plot to acquire the reference volume, VND, from which we calculated the BPND. Acute pharmacological challenge with amphetamine induced a significant decline of [(11)C]yohimbine BPND of ~38% in all volumes of interest. The BPND was greatest in the thalamus and striatum, followed in descending order by, frontal cortex, pons, and cerebellum. The experimental data demonstrate that [(11)C]yohimbine binding is sensitive to a challenge known to increase the extracellular level of noradrenaline, which can benefit future PET investigations of pathologic conditions related to disrupted noradrenergic neurotransmission.
我们对大鼠脑中[¹¹C]育亨宾与α-2肾上腺素能受体的结合潜能（BPND）进行了定量，以评估[¹¹C]育亨宾作为去甲肾上腺素能神经传递的体内标志物，并检验其对去甲肾上腺素水平的敏感性。对5只Sprague Dawley大鼠在基线状态下进行了双次[¹¹C]育亨宾动态正电子发射断层扫描（PET）记录，随后急性给予苯丙胺（2mg/kg）以诱导内源性去甲肾上腺素水平升高。使用带有动脉血浆输入的Logan图获得[¹¹C]育亨宾的分布容积（VT）。由于α-2肾上腺素能受体分布于全脑，缺乏无可置换结合的解剖区域使得BPND的估算变得复杂。我们使用抑制图来获取参考容积VND，并由此计算BPND。苯丙胺的急性药理学刺激导致所有感兴趣容积中[¹¹C]育亨宾BPND显著下降约38%。BPND在丘脑和纹状体中最高，其次依次为额叶皮质、脑桥和小脑。实验数据表明，[¹¹C]育亨宾结合对已知可增加细胞外去甲肾上腺素水平的刺激敏感，这将有利于未来对与去甲肾上腺素能神经传递中断相关的病理状况进行PET研究。
