In Vivo Quantitation of Glucose Metabolism in Mice Using Small-Animal PET and a Microfluidic Device

Abstract

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 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. Results: The studies showed that small (;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, and k à 4 , obtained for the 4 mouse brains, were comparable. The cerebral glucose metabolic rates obtained from 4 normoglycemic mice were 21.5 6 4.3 mmol/min/100 g (mean 6 SD) under the influence of 1.5% isoflurane. By generating the whole-body parametric images of K à 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. Conclusion: 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.

In vivo PET imaging with [18F]FDG to explain improved glucose uptake in an apolipoprotein A-I treated mouse model of diabetes

“…The FDG twotissue compartment model requires the plasma input function. The blood input function was converted to the plasma input function using the following equation [17]:…”

Image-Derived Input Function from the Vena Cava for18F-FDG PET Studies in Rats and Mice

“…New microfluidic blood sampling devices were developed to minimize the amount of blood withdrawn (3). Another method minimizing blood losses is the use of an arteriovenous shunt, coupled with either a g coincidence counter (4) or a b probe (5).…”

Noninvasive Measurement of Mouse Myocardial Glucose Uptake with 18F-FDG

“…Slower glucose transport rates result in lower erythrocyte-to-plasma glucose distribution ratios in nonhuman primates; ratios ranged from 0 in pigs to 0.45 in calves (4). More recently, Wu et al confirmed that 18 F-FDG transport was also slow in mice; the 18 F-FDG concentration in plasma was initially significantly higher than in whole blood and did not reach steady state until approximately 20 min after injection (6). There was little animal-to-animal variability; estimation of plasma 18 F-FDG from whole blood values was possible using an empirically derived exponential function, but this would need validation for different experimental conditions such as diabetes (6).…”