Awake nonhuman primate brain PET imaging with minimal head restraint: evaluation of GABAA-benzodiazepine binding with 11C-flumazenil in awake and anesthetized animals.
Awake nonhuman primate brain PET imaging with minimal head restraint: evaluation of GABAA-benzodiazepine binding with 11C-flumazenil in awake and anesthetized animals.
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DOI：
10.2967/jnumed.113.122077
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发表时间：
2013-11
期刊：
影响因子：
--
通讯作者：
Carson RE
中科院分区：
文献类型：
--
作者：
Sandiego CM;Jin X;Mulnix T;Fowles K;Labaree D;Ropchan J;Huang Y;Cosgrove K;Castner SA;Williams GV;Wells L;Rabiner EA;Carson RE
非人灵长类动物（NHP）的神经受体成像对于人类的转化研究方法是有价值的。然而，大多数NHP研究是在麻醉下进行的，这影响了受体结合措施的可解释性。本研究的目的是开发清醒的NHP成像与最小的头部约束，并比较在体内结合的GABA-苯二氮卓类放射性示踪剂[11 C]氟马西尼在麻醉和清醒条件下。我们假设，[11 C]氟马西尼结合潜力（BPND）将在异氟烷麻醉的猴子更高。将Focus-220小动物PET扫描仪安装到机械装置上，该机械装置将扫描仪升高并倾斜45°，而清醒的NHP在定制椅子上向后倾斜35°，以获得最佳的大脑定位。这需要动物适应椅子、触摸屏任务、静脉导管插入和倾斜。对于PET研究，使用推注加恒定输注（B/I）方法进行[11 C]氟马西尼给药。在清醒（n=6次扫描）和异氟烷麻醉（n=4次扫描）条件下扫描两只恒河猴。Vicra红外摄像机用于在PET扫描期间跟踪头部运动。在清醒状态下，采集注射后40-75分钟的发射和头部运动跟踪数据。麻醉猴扫描90分钟。皮质醇测量期间获得清醒和麻醉扫描。平衡分析用于麻醉（n=4）和清醒（n=5）数据集，以计算NHP模板空间中的平均BPND图像，使用脑桥作为参考区域。计算高和低结合区域中放射性浓度的每分钟变化百分比（%Δ/min），以评估平衡质量。猴适应NHP椅中进行清醒PET成像所需的程序。清醒和麻醉条件下的图像质量相当。清醒时与麻醉时的BPND值之间的关系为：BPND（清醒）=0.94BPND（麻醉）+0.36，r2=0.95。皮质醇水平在清醒状态下显著升高（p<0.05）。我们成功地进行了清醒NHP成像与最小的头部约束。清醒和麻醉条件下[11 C]氟马西尼BPND值接近一致。
Neuroreceptor imaging in the nonhuman primate (NHP) is valuable for translational research approaches in humans. However, the majority of NHP studies are conducted under anesthesia, which affects the interpretability of receptor binding measures. The aims of this study are to develop awake NHP imaging with minimal head restraint and to compare in vivo binding of GABAA-benzodiazepine radiotracer [11C]flumazenil under anesthetized and awake conditions. We hypothesized that [11C]flumazenil binding potential (BPND) would be higher in isoflurane-anesthetized monkeys. The Focus-220 small animal PET scanner was fitted to a mechanical device that raised and tilted the scanner 45° while the awake NHP was tilted back 35° in a custom chair for optimal brain positioning. This required acclimation of the animals to the chair, touch-screen tasks, i.v. catheter insertion, and tilting. For PET studies, the bolus plus constant infusion (B/I) method was used for [11C]flumazenil administration. Two rhesus monkeys were scanned under the awake (n=6 scans) and isoflurane-anesthetized (n=4 scans) conditions. The Vicra infrared camera was used to track head motion during PET scans. Under the awake condition, emission and head motion-tracking data were acquired for 40-75 min post-injection. Anesthetized monkeys were scanned for 90 min. Cortisol measurements were acquired during awake and anesthetized scans. Equilibrium analysis was used for both the anesthetized (n=4) and awake (n=5) datasets to compute mean BPND images in NHP template space, using the pons as a reference region. Percent change per min (%Δ/min) in radioactivity concentration was calculated in high and low binding regions to assess the quality of equilibrium. The monkeys acclimated to procedures in the NHP chair necessary to perform awake PET imaging. Image quality was comparable between awake and anesthetized conditions. The relationship between awake and anesthetized values was BPND(awake)=0.94BPND(anesthetized)+0.36, r2=0.95. Cortisol levels were significantly higher under the awake condition (p<0.05). We successfully performed awake NHP imaging with minimal head restraint. There was close agreement in [11C]flumazenil BPND values between awake and anesthetized conditions.
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4.8
作者：
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