Quantification of cerebral glucose metabolic rate in mice using 18F-FDG and small-animal PET.
The aim of this study was to evaluate various methods for estimating the metabolic rate of glucose utilization in the mouse brain (cMR(glc)) using small-animal PET and reliable blood curves derived by a microfluidic blood sampler. Typical values of (18)F-FDG rate constants of normal mouse cerebral cortex were estimated and used for cMR(glc) calculations. The feasibility of using the image-derived liver time-activity curve as a surrogate input function in various quantification methods was also evaluated.


METHODS
Thirteen normoglycemic C57BL/6 mice were studied. Eighteen blood samples were taken from the femoral artery by the microfluidic blood sampler. Tissue time-activity curves were derived from PET images. cMR(glc) values were calculated using 2 different input functions (one derived from the blood samples [IF(blood)] and the other from the liver time-activity curve [IF(liver)]) in various quantification methods, which included the 3-compartment (18)F-FDG model (from which the (18)F-FDG rate constants were derived), the Patlak analysis, and operational equations. The estimated cMR(glc) value based on IF(blood) and the 3-compartment model served as a standard for comparisons with the cMR(glc) values calculated by the other methods.


RESULTS
The values of K(1), k(2), k(3), k(4), and K(FDG) estimated by IF(blood) and the 3-compartment model were 0.22 +/- 0.05 mL/min/g, 0.48 +/- 0.09 min(-1), 0.06 +/- 0.02 min(-1), 0.025 +/- 0.010 min(-1), and 0.024 +/- 0.007 mL/min/g, respectively. The standard cMR(glc) value was, therefore, 40.6 +/- 13.3 micromol/100 g/min (lumped constant = 0.6). No significant difference between the standard cMR(glc) and the cMR(glc) estimated by the operational equation that includes k(4) was observed. The standard cMR(glc) was also found to have strong correlations (r > 0.8) with the cMR(glc) value estimated by the use of IF(liver) in the 3-compartment model and with those estimated by the Patlak analysis (using either IF(blood) or IF(liver)).


CONCLUSIONS
The (18)F-FDG rate constants of normal mouse cerebral cortex were determined. These values can be used in the k(4)-included operational equation to calculate cMR(glc). IF(liver) can be used to estimate cMR(glc) in most methods included in this study, with proper linear corrections applied. The validity of using the Patlak analysis for estimating cMR(glc) in mouse PET studies was also confirmed.
Yu
Amy S
AS
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California 90095-6948, USA.
Lin
Hong-Dun
HD
Huang
Sung-Cheng
SC
Phelps
Michael E
ME
Wu
Hsiao-Ming
HM
D000818:Animals; D001921:Brain / Q000378:metabolism*; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals
D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose