Wu Hsiao-Ming, Sui Guodong, Lee Cheng-Chung, Prins Mayumi L, Ladno Waldemar, Lin Hong-Dun, Yu Amy S, Phelps Michael E, Huang Sung-Cheng
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095-6948, USA.
J Nucl Med. 2007 May;48(5):837-45. doi: 10.2967/jnumed.106.038182.
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.
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 (18)F-FDG and input functions derived from the blood samples taken by the new device. (18)F-FDG kinetics in the mouse brain and myocardial tissues were analyzed.
The studies showed that small ( approximately 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 (18)F-FDG 3-compartment model and >0.99 for Patlak analysis. The (18)F-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 mumol/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 (18)F-FDG, we obtained similar pixel values as those obtained from the conventional regional analysis using tissue time-activity curves.
With an automated microfluidic 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.
从小动物身上采集血液的挑战阻碍了定量小动物正电子发射断层扫描（PET）的实现。需要克服与传统血液采样程序相关的困难，以便在小鼠中充分利用这项技术。
我们在集成微流控平台上开发了一种自动血液采样装置，用于从小鼠身上采集少量血液样本。我们展示了使用（18）F - FDG以及由新装置采集的血液样本得出的输入函数进行定量小动物PET研究的可行性。分析了（18）F - FDG在小鼠脑和心肌组织中的动力学。
研究表明，无需用户直接干预，即可从小鼠身上准确采集体积小（约220纳升）且时间精确的血液样本。动物的总失血量小于体重的0.5%，并且研究人员受到的辐射暴露降至最低。当从18个连续血液样本得出输入函数时，脑和心肌组织时间 - 活度曲线获得了良好的模型拟合。使用（18）F - FDG三室模型时曲线拟合的R（2）值大于0.90，Patlak分析时大于0.99。从4只小鼠脑获得的（18）F - FDG速率常数K（1）（）、k（2）（）、k（3）（）和k（4）（）具有可比性。在1.5%异氟烷影响下，4只血糖正常小鼠的脑葡萄糖代谢率为21.5±4.3微摩尔/分钟/100克（平均值±标准差）。通过生成K（FDG）（*）（毫升/分钟/克）（（18）F - FDG的摄取常数）的全身参数图像，我们获得了与使用组织时间 - 活度曲线进行传统区域分析所获得的像素值相似的值。
通过自动微流控血液采样装置，我们的研究表明，在小动物PET设施中，可以在小鼠中常规、可靠且安全地进行定量小动物PET。
