Yang Feng-Yi, Chang Wen-Yuan, Chen Jyh-Cheng, Lee Lin-Chien, Hung Yi-Shun
Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan; Biophotonics and Molecular Imaging Research Center, National Yang-Ming University, Taipei, Taiwan.
Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
Neuroimage. 2014 Apr 15;90:93-8. doi: 10.1016/j.neuroimage.2013.12.033. Epub 2013 Dec 22.
The goal of this study was to evaluate the pharmacokinetics of (18)F-2-fluoro-2-deoxy-d-glucose ((18)F-FDG) and the expression of glucose transporter 1 (GLUT1) protein after blood-brain barrier (BBB) disruption of normal rat brains by focused ultrasound (FUS). After delivery of an intravenous bolus of ~37 MBq (1 mCi) (18)F-FDG, dynamic positron emission tomography scans were performed on rats with normal brains and those whose BBBs had been disrupted by FUS. Arterial blood sampling was collected throughout the scanning procedure. A 2-tissue compartmental model was used to estimate (18)F-FDG kinetic parameters in brain tissues. The rate constants Ki, K1, and k3 were assumed to characterize the uptake, transport, and hexokinase activity, respectively, of (18)F-FDG. The uptake of (18)F-FDG in brains significantly decreased immediately after the blood-brain barrier was disrupted. At the same time, the derived values of Ki, K1, and k3 for the sonicated brains were significantly lower than those for the control brains. In agreement with the reduction in glucose, Western blot analyses confirmed that focused ultrasound exposure significantly reduced the expression of GLUT1 protein in the brains. Furthermore, the effect of focused ultrasound on glucose uptake was transient and reversible 24h after sonication. Our results indicate that focused ultrasound may inhibit GLUT1 expression to decrease the glucose uptake in brain tissue during the period of BBB disruption.
本研究的目的是评估聚焦超声（FUS）破坏正常大鼠血脑屏障（BBB）后，（18）F-2-氟-2-脱氧-D-葡萄糖（（18）F-FDG）的药代动力学以及葡萄糖转运蛋白1（GLUT1）的表达。静脉注射约37 MBq（1 mCi）的（18）F-FDG后，对正常大鼠和血脑屏障已被FUS破坏的大鼠进行动态正电子发射断层扫描。在整个扫描过程中采集动脉血样本。采用二室模型估计脑组织中（18）F-FDG的动力学参数。速率常数Ki、K1和k3分别被认为可表征（18）F-FDG的摄取、转运和己糖激酶活性。血脑屏障破坏后，脑中（18）F-FDG的摄取立即显著降低。同时，超声处理组脑的Ki、K1和k3推导值显著低于对照组脑。与葡萄糖减少一致，蛋白质免疫印迹分析证实聚焦超声照射显著降低了脑中GLUT1的表达。此外，聚焦超声对葡萄糖摄取的影响在超声处理后24小时是短暂且可逆的。我们的结果表明，聚焦超声可能通过抑制GLUT1的表达，在血脑屏障破坏期间减少脑组织中的葡萄糖摄取。
