Marsteller Douglas A, Barbarich-Marsteller Nicole C, Fowler Joanna S, Schiffer Wynne K, Alexoff David L, Rubins Daniel J, Dewey Stephen L
Graduate Program in Molecular and Cellular Pharmacology, SUNY Stony Brook, NY 11794-8651, USA.
Nucl Med Biol. 2006 Jan;33(1):71-9. doi: 10.1016/j.nucmedbio.2005.09.003.
One strength of small animal imaging is the ability to obtain longitudinal measurements within the same animal, effectively reducing the number of animals needed and increasing statistical power. However, the variability of within-rodent brain glucose uptake after an intraperitoneal injection across an extended time has not been measured.
Small animal imaging with 2-deoxy-2-[(18)F]-fluoro-D-glucose ((18)FDG) was used to determine the variability of a 50-min brain (18)FDG uptake following an intraperitoneal injection over time in awake male and female Sprague-Dawley rodents.
After determining the variability of an intraperitoneal injection in the awake rat, we found that normalization of brain (18)FDG uptake for (1) injected dose and body weight or (2) body weight, plasma glucose concentration and injected dose resulted in a coefficient of variation (CV) of 15%. However, if we normalized regional uptake to whole brain to compare relative regional changes, the CV was less than 5%. Normalized cerebral (18)FDG uptake values were reproducible for a 2-week period in young adult animals. After 1 year, both male and female animals had reduced whole-brain uptake, as well as reduced regional hippocampal and striatal (18)FDG uptake.
Overall, our results were similar to findings in previous rodent and human clinical populations; thus, using a high throughput study with intraperitoneal (18)FDG is a promising preclinical model for clinical populations. This is particularly relevant for measuring changes in brain function after experimental manipulation, such as long-term pharmacological administration.
小动物成像的一个优势在于能够在同一只动物体内进行纵向测量，从而有效减少所需动物的数量并提高统计效能。然而，腹腔注射后较长时间内啮齿动物脑内葡萄糖摄取的变异性尚未得到测量。
采用2-脱氧-2-[(18)F]-氟-D-葡萄糖（(18)FDG）小动物成像技术，测定清醒的雄性和雌性Sprague-Dawley啮齿动物腹腔注射后50分钟脑内(18)FDG摄取随时间的变异性。
在确定清醒大鼠腹腔注射的变异性后，我们发现，将脑(18)FDG摄取量按以下两种方式进行归一化处理：(1)注射剂量和体重，或(2)体重、血浆葡萄糖浓度和注射剂量，变异系数（CV）为15%。然而，如果我们将区域摄取量相对于全脑进行归一化以比较相对区域变化，则CV小于5%。在年轻成年动物中，归一化的脑(18)FDG摄取值在2周内具有可重复性。1年后，雄性和雌性动物的全脑摄取均减少，海马体和纹状体区域的(18)FDG摄取也减少。
总体而言，我们的结果与先前啮齿动物和人类临床群体的研究结果相似；因此，使用腹腔注射(18)FDG的高通量研究是一种有前景的临床前模型。这对于测量实验操作（如长期药物给药）后脑功能的变化尤为重要。
