Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
J Nucl Med. 2011 May;52(5):800-7. doi: 10.2967/jnumed.110.085092. Epub 2011 Apr 15.
The effects of dietary condition and blood glucose level on the kinetics and uptake of (18)F-FDG in mice were systematically investigated using intraperitoneal and tail-vein injection.
Dynamic PET was performed for 60 min on 23 isoflurane-anesthetized male C57BL/6 mice after intravenous (n = 11) or intraperitoneal (n = 12) injection of (18)F-FDG. Five and 6 mice in the intravenous and intraperitoneal groups, respectively, were kept fasting overnight (18 ± 2 h), and the others were fed ad libitum. Serial blood samples were collected from the femoral artery to measure (18)F-FDG and glucose concentrations. Image data were reconstructed using filtered backprojection with CT-based attenuation correction. The standardized uptake value (SUV) was estimated from the 45- to 60-min image. The metabolic rate of glucose (MRGlu) and (18)F-FDG uptake constant (K(i)) were derived by Patlak graphical analysis.
In the brain, SUV and K(i) were significantly higher in fasting mice with intraperitoneal injection, but MRGlu did not differ significantly under different dietary states and administration routes. Cerebral K(i) was inversely related to elevated blood glucose levels, irrespective of administration route or dietary state. In myocardium, SUV, K(i), and MRGlu were significantly lower in fasting than in nonfasting mice for both routes of injection. Myocardial SUV and K(i) were strongly dependent on the dietary state, and K(i) did not correlate with the blood glucose level. Similar results were obtained for skeletal muscle, although the differences were not as pronounced.
Intraperitoneal injection is a valid alternative route, providing pharmacokinetic data equivalent to data from tail-vein injection for small-animal (18)F-FDG PET. Cerebral K(i) varies inversely with blood glucose level, but the measured cerebral MRGlu does not correlate with blood glucose level or dietary condition. Conversely, the K(i) values of the myocardium and skeletal muscle are strongly dependent on dietary condition but not on blood glucose level. In tissue in which (18)F-FDG uptake declines with increasing blood glucose, correction for blood glucose level will make SUV a more robust outcome measure of MRGlu.
本研究通过腹腔内和尾静脉注射，系统地研究了饮食状况和血糖水平对小鼠（18）F-FDG 摄取动力学和摄取的影响。
23 只异氟烷麻醉的雄性 C57BL/6 小鼠静脉（n = 11）或腹腔内（n = 12）注射（18）F-FDG 后，进行 60 分钟的动态 PET。静脉内和腹腔内组中分别有 5 只和 6 只小鼠禁食过夜（18 ± 2 h），其余小鼠自由进食。从股动脉采集连续血样，以测量（18）F-FDG 和葡萄糖浓度。使用基于 CT 的衰减校正的滤波反投影重建图像数据。从 45 到 60 分钟的图像中估算标准化摄取值（SUV）。通过 Patlak 图形分析得出葡萄糖代谢率（MRGlu）和（18）F-FDG 摄取常数（K（i））。
在大脑中，腹腔内注射的禁食小鼠的 SUV 和 K（i）明显升高，但不同饮食状态和给药途径下的 MRGlu 没有显著差异。脑内 K（i）与升高的血糖水平呈负相关，与给药途径或饮食状态无关。在心肌中，与非禁食小鼠相比，两种注射途径的禁食小鼠的 SUV、K（i）和 MRGlu 均显著降低。心肌 SUV 和 K（i）强烈依赖于饮食状态，而 K（i）与血糖水平无关。在骨骼肌中也得到了类似的结果，尽管差异不那么明显。
腹腔内注射是一种有效的替代途径，为小动物（18）F-FDG PET 提供了与尾静脉注射等效的药代动力学数据。脑内 K（i）与血糖水平呈负相关，但测量的脑内 MRGlu 与血糖水平或饮食状态无关。相反，心肌和骨骼肌的 K（i）值强烈依赖于饮食状态，但不受血糖水平的影响。在（18）F-FDG 摄取随血糖升高而降低的组织中，校正血糖水平将使 SUV 成为更稳健的 MRGlu 结局测量指标。
