In vivo quantitation of glucose metabolism in mice using small-animal PET and a microfluidic device.

ABSTRACT

UNLABELLED 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 ( 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. 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.