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

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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 18F-FDG and input functions derived from the blood samples taken by the new device. 18F-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 0.90 using a 18F-FDG 3-compartment model and >0.99 for Patlak analysis. The 18F-FDG rate constants , , , and , obtained for the 4 mouse brains, were comparable. The cerebral glucose metabolic rates obtained from 4 normoglycemic mice were 21.5 ± 4.3 μmol/min/100 g (mean ± SD) under the influence of 1.5% isoflurane. By generating the whole-body parametric images of (mL/min/g), the uptake constant of 18F-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.

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