Evaluation of cannabinoid type 1 receptor expression in the rat brain using [18F]MK-9470 microPET
Evaluation of cannabinoid type 1 receptor expression in the rat brain using [18F]MK-9470 microPET
复制标题
使用 [18F]MK-9470 microPET 评估大鼠脑中大麻素 1 型受体的表达
DOI：
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发表时间：
2013
影响因子：
9.1
通讯作者：
M. Schreckenberger
中科院分区：
文献类型：
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作者：
I. Miederer;S. Maus;I. Zwiener;Ganna Podoprygorina;D. Meshcheryakov;B. Lutz;M. Schreckenberger
[18 F]MK-9470是一种与大麻素1型（CB 1）受体特异性结合的反向激动剂。在这项研究中，CB 1受体分布在大鼠brain.MethodsTwo C57 BL/6 N小鼠（一个CB 1-/-和一个野生型）和19 Sprague道利大鼠的调查，采用Focus 120 microPET扫描仪的半定量采集和分析协议。7只大鼠扫描两次进行重测评价，6只大鼠扫描使用反向CB 1受体激动剂利莫那班进行阻断实验，19只大鼠扫描进行基线研究。计算每毫升注射剂量百分比（%ID/ml）或摄取比（VOI目标/VOI全脑）。计算Bland-Altman图，并使用双侧配对t检验比较平均值。结果比较CB 1 −/−小鼠和野生型小鼠的数据，[18 F]MK-9470显示出良好的特异性。关于大鼠数据，试验和重复试验测量值之间的差异或其平均值之间无相关性。检验和复检数据显示出强相关性（ρc = 0.846，p ≤ 0.01; rPearson = 0.857）。并未发现所有区域都具有等效性，甚至在基线或阻断条件下的脑桥中也没有发现。仅基线研究显示尾壳核和丘脑的摄取水平最高，而海马、下丘脑和小脑的摄取水平中等，皮质、杏仁核和脑桥的摄取水平最低。然而，所提出的使用参数摄取率的分析方法是简单的，并且提供稳定的结果，允许区分不同的脑区域。
PurposeThe ligand [18F]MK-9470 is an inverse agonist binding with high affinity and specificity to the cannabinoid type 1 (CB1) receptor. In this study, a semiquantitative acquisition and analysis protocol for investigation of the CB1 receptor distribution in the rat brain was established.MethodsTwo C57BL/6N mice (one CB1−/− and one wild-type) and 19 Sprague Dawley rats were investigated using a Focus 120 microPET scanner. Seven rats were scanned twice for test–retest evaluation, six rats were scanned for blocking experiments using the inverse CB1 receptor agonist rimonabant, and 19 rats were scanned for baseline studies. Percentage injected dose per millilitre (%ID/ml) or uptake ratios (VOItarget/VOIwhole brain) were calculated. A Bland-Altman-plot was computed and mean values were compared using a two-sided paired t test.ResultsComparing the data from the CB1−/− mouse and the wild-type mouse, [18F]MK-9470 showed good specificity. Regarding the rat data, there was no relationship between the difference between the test and retest measurements or their mean value. The test and retest data showed a strong correlation (ρc = 0.846, p ≤ 0.01; rPearson = 0.857). Equivalence was not found for all regions and not even in the pons at baseline or under blocking condition. Only the baseline studies showed the highest levels of uptake in the caudate-putamen and thalamus, whereas moderate uptake was found in the hippocampus, hypothalamus and cerebellum, and the lowest uptake was observed in the cortex, amygdala and pons.ConclusionA reference region is not available; however, the proposed analysis method using the parameter uptake ratio is simple and delivers stable results allowing the discrimination of distinct brain regions.
影响因子：
6.7
作者：
Fan, Hong;Kotsikorou, Evangelia;Horti, Andrew G.
通讯作者：
Horti, Andrew G.
影响因子：
13.9
作者：
Katona I;Freund TF
通讯作者：
Freund TF