In vivo quantitation of glucose metabolism in mice using small-animal PET and a microfluidic device
In vivo quantitation of glucose metabolism in mice using small-animal PET and a microfluidic device
复制标题
DOI：
10.2967/jnumed.106.038182
复制
发表时间：
2007-05-01
影响因子：
9.3
通讯作者：
Huang, Sung-Cheng
中科院分区：
文献类型：
--
作者：
Wu, Hsiao-Ming;Sui, Guodong;Huang, Sung-Cheng
从小动物身上采集血液的挑战阻碍了定量小动物PET的实现。与传统的血液采样程序相关的困难需要克服，以促进这种技术在小鼠中的充分使用。方法：我们在集成微流控平台上开发了一种自动采血装置，用于从小鼠体内抽取少量血液样品。我们证明了使用F-18-FDG进行定量小动物PET研究的可行性，并从新设备采集的血液样本中获得输入函数。分析了小鼠脑和心肌组织中F-18-FDG的动力学。结果如下：研究表明，可以在没有直接用户干预的情况下从小鼠中准确地采集少量（类似于220 nL）血液样本。动物的总失血量<体重的0.5%，研究人员的辐射暴露最小化。当输入函数来自18个系列血液样本时，获得了与大脑和心肌组织时间-活动曲线的良好模型拟合。使用F-18-FDG三房室模型的曲线拟合的R-2值> 0.90，并且对于Patlak分析的R-2值> 0.99。从4只小鼠脑中获得的F-18-FDG速率常数K-1*、k（2）*、k（3）* 和k（4），* 是相当的。在1.5%异氟烷的影响下，从4只血糖正常小鼠中获得的脑葡萄糖代谢率为21.5 +/- 4.3 μ mol/min/100 g（平均值+/- SD）。通过生成F-18-FDG的摄取常数K*（FDG）（mL/min/g）的全身参数图像，我们获得了与使用组织时间-活性曲线从常规区域分析获得的像素值相似的像素值。结论：我们的研究表明，使用自动微流控血液采样装置，可以在小动物PET设施中对小鼠进行常规、可靠和安全的定量小动物PET。
The challenge of sampling blood from small animals has hampered the realization of quantitative small-animal PET. Difficulties associated with the conventional blood-sampling procedure need to be overcome to facilitate the full use of this technique in mice. Methods: We developed an automated blood-sampling device on an integrated microfluidic platform to withdraw small blood samples from mice. We demonstrate the feasibility of performing quantitative small-animal PET studies using F-18-FDG and input functions derived from the blood samples taken by the new device. F-18-FDG kinetics in the mouse brain and myocardial tissues were analyzed. Results: The studies showed that small (similar to 220 nL) blood samples can be taken accurately in volume and precisely in time from the mouse without direct user intervention. The total blood loss in the animal was < 0.5% of the body weight, and radiation exposure to the investigators was minimized. Good model fittings to the brain and the myocardial tissue time-activity curves were obtained when the input functions were derived from the 18 serial blood samples. The R-2 values of the curve fittings are > 0.90 using a F-18-FDG 3-compartment model and > 0.99 for Patlak analysis. The F-18-FDG rate constants K-1*, k(2)*, k(3)*, and k(4),*,obtained for the 4 mouse brains, were comparable. The cerebral glucose metabolic rates obtained from 4 normoglycemic mice were 21.5 +/- 4.3 mu mol/min/100 g (mean +/- SD) under the influence of 1.5% isoflurane. By generating the whole-body parametric images of K*(FDG) (mL/min/g), the uptake constant of F-18-FDG, we obtained similar pixel values as those obtained from the conventional regional analysis using tissue time-activity curves. Conclusion: With an automated microfluiclic blood-sampling device, our studies showed that quantitative small-animal PET can be performed in mice routinely, reliably, and safely in a small-animal PET facility.