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


CONCLUSIONS
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.
Wu
Hsiao-Ming
HM
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095-6948, USA. cwu@mednet.ucla.edu
Sui
Guodong
G
Lee
Cheng-Chung
CC
Prins
Mayumi L
ML
Ladno
Waldemar
W
Lin
Hong-Dun
HD
Yu
Amy S
AS
Phelps
Michael E
ME
Huang
Sung-Cheng
SC
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D006321:Heart / Q000000981:diagnostic imaging; D007089:Image Enhancement / Q000295:instrumentation / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000295:instrumentation / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D044085:Microfluidics / Q000295:instrumentation* / Q000379:methods; D009206:Myocardium / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000295:instrumentation* / Q000379:methods
D019788:Fluorodeoxyglucose F18