[11C]NE40 作为一种 2 型大麻素受体 PET 示踪剂的临床前评估。
Preclinical evaluation of [11C]NE40, a type 2 cannabinoid receptor PET tracer.
机构信息
Laboratory for Radiopharmacy, K.U. Leuven, Leuven, Belgium BE3000.
出版信息
Nucl Med Biol. 2012 Apr;39(3):389-99. doi: 10.1016/j.nucmedbio.2011.09.005. Epub 2011 Dec 11.
INTRODUCTION
Up-regulation of the type 2 cannabinoid receptor (CB(2)R) has been reported in (neuro)inflammatory diseases. In this study, we report the preclinical evaluation of [(11)C]NE40 as positron emission tomography (PET) radioligand for visualization of the CB(2)R.
METHODS
The selectivity of NE40 for CB(2)R and its toxicity and mutagenicity were determined. [(11)C]NE40 was evaluated by biodistribution and autoradiography studies in normal rats and a microPET study in normal mice, rats and a rhesus monkey. Specific in vivo binding of [(11)C]NE40 to human CB(2)R (hCB(2)R) was studied in a rat model with hCB(2)R overexpression.
RESULTS
[(11)C]NE40 shows specific CB(2)R binding in the spleen and blood of normal rats and high brain uptake in rhesus monkey. [(11)C]NE40 showed specific and reversible binding to hCB(2)R in vivo in a rat model with local hCB(2)R overexpression.
CONCLUSIONS
[(11)C]NE40 shows favorable characteristics as radioligand for in vivo visualization of the CB(2)R and is a promising candidate for hCB(2)R PET imaging.
简介
在（神经）炎症性疾病中，已经报道了 2 型大麻素受体（CB2R）的上调。在这项研究中，我们报告了 [(11)C]NE40 作为正电子发射断层扫描（PET）放射性配体用于可视化 CB2R 的临床前评估。
方法
确定了 NE40 对 CB2R 的选择性及其毒性和致突变性。通过在正常大鼠中的生物分布和放射性自显影研究以及在正常小鼠、大鼠和恒河猴中的 microPET 研究评估了 [(11)C]NE40。在 hCB2R 过表达的大鼠模型中研究了 [(11)C]NE40 与人 CB2R（hCB2R）的特异性体内结合。
结果
[(11)C]NE40 在正常大鼠的脾脏和血液中显示出特异性的 CB2R 结合，在恒河猴的大脑中摄取量较高。在局部 hCB2R 过表达的大鼠模型中，[(11)C]NE40 在体内显示出特异性和可逆的 hCB2R 结合。
结论
[(11)C]NE40 作为 CB2R 体内可视化的放射性配体具有良好的特性，是 hCB2R PET 成像的有前途的候选物。
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