Absolute quantification of regional cerebral glucose utilization in mice by 18F-FDG small animal PET scanning and 2-14C-DG autoradiography.
The purpose of this study was to evaluate the feasibility of absolute quantification of regional cerebral glucose utilization (rCMR(glc)) in mice by use of (18)F-FDG and a small animal PET scanner. rCMR(glc) determined with (18)F-FDG PET was compared with values determined simultaneously by the autoradiographic 2-(14)C-DG method. In addition, we compared the rCMR(glc) values under isoflurane, ketamine and xylazine anesthesia, and awake states.


METHODS
Immediately after injection of (18)F-FDG and 2-(14)C-DG into mice, timed arterial samples were drawn over 45 min to determine the time courses of (18)F-FDG and 2-(14)C-DG. Animals were euthanized at 45 min and their brain was imaged with the PET scanner. The brains were then processed for 2-(14)C-DG autoradiography. Regions of interest were manually placed over cortical regions on corresponding coronal (18)F-FDG PET and 2-(14)C-DG autoradiographic images. rCMR(glc) values were calculated for both tracers by the autoradiographic 2-(14)C-DG method with modifications for the different rate and lumped constants for the 2 tracers.


RESULTS
Average rCMR(glc) values in cerebral cortex with (18)F-FDG PET under normoglycemic conditions (isoflurane and awake) were generally lower (by 8.3%) but strongly correlated with those of 2-(14)C-DG (r(2) = 0.95). On the other hand, under hyperglycemic conditions (ketamine/xylazine) average cortical rCMR(glc) values with (18)F-FDG PET were higher (by 17.3%) than those with 2-(14)C-DG. Values for rCMR(glc) and uptake (percentage injected dose per gram [%ID/g]) with (18)F-FDG PET were significantly lower under both isoflurane and ketamine/xylazine anesthesia than in the awake mice. However, the reductions of rCMR(glc) were markedly greater under isoflurane (by 57%) than under ketamine and xylazine (by 19%), whereas more marked reductions of %ID/g were observed with ketamine/xylazine (by 54%) than with isoflurane (by 37%). These reverse differences between isoflurane and ketamine/xylazine may be due to competitive effect of (18)F-FDG and glucose uptake to the brain under hyperglycemia.


CONCLUSIONS
We were able to obtain accurate absolute quantification of rCMR(glc) with mouse (18)F-FDG PET imaging as confirmed by concurrent use of the autoradiographic 2-(14)C-DG method. Underestimation of rCMR(glc) by (18)F-FDG in normoglycemic conditions may be due to partial-volume effects. Computation of rCMR(glc) from (18)F-FDG data in hyperglycemic animals may require, however, alternative rate and lumped constants for (18)F-FDG.
Toyama
Hiroshi
H
Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA. htoyama@fujita-hu.ac.jp
Ichise
Masanori
M
Liow
Jeih-San
JS
Modell
Kendra J
KJ
Vines
Douglass C
DC
Esaki
Takanori
T
Cook
Michelle
M
Seidel
Jurgen
J
Sokoloff
Louis
L
Green
Michael V
MV
Innis
Robert B
RB
D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000166:cytology / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D001931:Brain Mapping / Q000379:methods; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D003847:Deoxyglucose / Q000493:pharmacokinetics; D005240:Feasibility Studies; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D005947:Glucose / Q000378:metabolism*; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000295:instrumentation / Q000379:methods*
D000777:Anesthetics; D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D003847:Deoxyglucose; D005947:Glucose