Department of Nuclear Medicine, University Hospital, University of Münster, Münster, Germany.
J Nucl Med. 2010 Aug;51(8):1269-76. doi: 10.2967/jnumed.110.074997.
Dysfunction of the sympathetic nervous system underlies many cardiac diseases and can be assessed by molecular imaging using PET in humans. Small-animal PET should enable noninvasive quantitation of the sympathetic nervous system in mouse models of human disease. For mice, however, the radioactivity needed to give acceptable image quality may be associated with a mass of unlabeled compound sufficient to block the binding of radioligand to its target. The present study assesses the feasibility of using [N-methyl-(11)C]meta-hydroxyephedrine ((11)C-mHED) to measure norepinephrine reuptake in humans, to determine cardiac innervation in mice.
Anesthetized mice were placed in a small-animal PET scanner. (11)C-mHED (containing 18% precursor metaraminol) was injected via a tail vein into each animal simultaneously. Fifteen minutes later, animals were injected with saline or metaraminol which competes with mHED for norepinephrine reuptake. (18)F-FDG was injected at 60 min to identify heart regions. After reconstruction of the list-mode data, radioactivity in myocardial regions was computed using in-house software, and time-activity curves were plotted.
Hearts were clearly visualized after injection of (11)C-mHED. Injection of metaraminol at doses less than 50 nmol x kg(-1) had no effect, whereas doses greater than 100 nmol x kg(-1) caused a dose-dependent loss of specifically bound radioactivity.
(11)C-mHED was successfully used to visualize and assess myocardial innervation in mice. Uptake of (11)C-mHED is displaceable by the false transmitter metaraminol. The total molar dose of metaraminol and (11)C-mHED must be considered in the analysis of PET data.
交感神经系统功能障碍是许多心脏疾病的基础，可以通过人类的正电子发射断层扫描（PET）分子成像进行评估。小动物 PET 应该能够无创地定量测量人类疾病小鼠模型中的交感神经系统。然而，对于老鼠来说，获得可接受的图像质量所需的放射性可能与足以阻止放射性配体与其靶标结合的未标记化合物的大量有关。本研究评估了使用[N-甲基-(11)C]间羟基苯丙胺（(11)C-mHED）测量人类去甲肾上腺素再摄取以确定小鼠心脏神经支配的可行性。
将麻醉的小鼠放入小动物 PET 扫描仪中。将 (11)C-mHED（含有 18%前体间羟胺）通过尾静脉同时注射到每只动物中。15 分钟后，给动物注射盐水或间羟胺，间羟胺与 mHED 竞争去甲肾上腺素再摄取。在 60 分钟时注射 (18)F-FDG 以识别心脏区域。对列表模式数据进行重建后，使用内部软件计算心肌区域的放射性，并绘制时间-活性曲线。
注射 (11)C-mHED 后，心脏清晰可见。注射剂量小于 50 nmol x kg(-1)的间羟胺没有影响，而剂量大于 100 nmol x kg(-1)则导致特异性结合放射性的剂量依赖性丧失。
(11)C-mHED 成功用于可视化和评估小鼠的心肌神经支配。摄取 (11)C-mHED 可被假递质间羟胺置换。在分析 PET 数据时，必须考虑间羟胺和 (11)C-mHED 的总摩尔剂量。
