Zhang Xuan, Paule Merle G, Newport Glenn D, Zou Xiaoju, Sadovova Natalya, Berridge Marc S, Apana Scott M, Hanig Joseph P, Slikker William, Wang Cheng
Division of Neurotoxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079, USA.
Toxicol Sci. 2009 Oct;111(2):355-61. doi: 10.1093/toxsci/kfp167. Epub 2009 Jul 28.
It has been reported that suppression of N-methyl-D-aspartate (NMDA) receptor function by ketamine may trigger apoptosis of neurons when given repeatedly during the brain growth spurt period. Because microPET scans can provide in vivo molecular imaging at sufficient resolution, it has been proposed as a minimally invasive method for detecting apoptosis using the tracer (18)F-labeled annexin V. In this study, the effect of ketamine on the metabolism and integrity of the rat brain were evaluated by investigating the uptake and retention of (18)F-fluorodeoxyglucose (FDG) and (18)F-annexin V using microPET imaging. On postnatal day (PND) 7, rat pups in the experimental group were exposed to six injections of ketamine (20 mg/kg at 2-h intervals) and control rat pups received six injections of saline. On PND 35, 37 MBq (1 mCi) of (18)F-FDG or (18)F-annexin V was injected into the tail vein of treated and control rats, and static microPET images were obtained over 1 (FDG) and 2 h (annexin V) following the injection. No significant difference was found in (18)F-FDG uptake in the regions of interest (ROIs) in the brains of ketamine-treated rats compared with saline-treated controls. The uptake of (18)F-annexin V, however, was significantly increased in the ROI of ketamine-treated rats. Additionally, the duration of annexin V tracer washout was prolonged in the ketamine-treated animals. These results demonstrate that microPET imaging is capable of distinguishing differences in retention of (18)F-annexin V in different brain regions and suggests that this approach may provide a minimally invasive biomarker of neuronal apoptosis in rats.
据报道，在脑发育快速期反复给予氯胺酮时，其对N-甲基-D-天冬氨酸（NMDA）受体功能的抑制可能会引发神经元凋亡。由于微型正电子发射断层扫描（microPET）能够以足够的分辨率提供体内分子成像，因此有人提出将其作为一种使用（18）F标记的膜联蛋白V检测凋亡的微创方法。在本研究中，通过使用微型正电子发射断层扫描成像研究（18）F-氟脱氧葡萄糖（FDG）和（18）F-膜联蛋白V的摄取和滞留情况，评估了氯胺酮对大鼠脑代谢和完整性的影响。在出生后第7天（PND7），实验组的幼鼠接受6次氯胺酮注射（20mg/kg，间隔2小时），对照幼鼠接受6次生理盐水注射。在PND35时，向处理组和对照组大鼠的尾静脉注射37MBq（1mCi）的（18）F-FDG或（18）F-膜联蛋白V，并在注射后1小时（FDG）和2小时（膜联蛋白V）获取静态微型正电子发射断层扫描图像。与生理盐水处理的对照组相比，氯胺酮处理的大鼠脑内感兴趣区域（ROI）的（18）F-FDG摄取没有显著差异。然而，氯胺酮处理的大鼠ROI中（18）F-膜联蛋白V的摄取显著增加。此外，氯胺酮处理的动物中膜联蛋白V示踪剂洗脱的持续时间延长。这些结果表明，微型正电子发射断层扫描成像能够区分不同脑区（18）F-膜联蛋白V滞留的差异，并表明这种方法可能为大鼠神经元凋亡提供一种微创生物标志物。
