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Basic Science Investigations |
1 Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland
2 Laboratory of Cerebral Metabolism, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland
3 Department of Nuclear Medicine, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland
The purpose of this study was to evaluate the feasibility of absolute quantification of regional cerebral glucose utilization (rCMRglc) in mice by use of 18F-FDG and a small animal PET scanner. rCMRglc determined with 18F-FDG PET was compared with values determined simultaneously by the autoradiographic 2-14C-DG method. In addition, we compared the rCMRglc values under isoflurane, ketamine and xylazine anesthesia, and awake states. Methods: Immediately after injection of 18F-FDG and 2-14C-DG into mice, timed arterial samples were drawn over 45 min to determine the time courses of 18F-FDG and 2-14C-DG. Animals were euthanized at 45 min and their brain was imaged with the PET scanner. The brains were then processed for 2-14C-DG autoradiography. Regions of interest were manually placed over cortical regions on corresponding coronal 18F-FDG PET and 2-14C-DG autoradiographic images. rCMRglc values were calculated for both tracers by the autoradiographic 2-14C-DG method with modifications for the different rate and lumped constants for the 2 tracers. Results: Average rCMRglc values in cerebral cortex with 18F-FDG PET under normoglycemic conditions (isoflurane and awake) were generally lower (by 8.3%) but strongly correlated with those of 2-14C-DG (r2 = 0.95). On the other hand, under hyperglycemic conditions (ketamine/xylazine) average cortical rCMRglc values with 18F-FDG PET were higher (by 17.3%) than those with 2-14C-DG. Values for rCMRglc and uptake (percentage injected dose per gram [%ID/g]) with 18F-FDG PET were significantly lower under both isoflurane and ketamine/xylazine anesthesia than in the awake mice. However, the reductions of rCMRglc 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 18F-FDG and glucose uptake to the brain under hyperglycemia. Conclusion: We were able to obtain accurate absolute quantification of rCMRglc with mouse 18F-FDG PET imaging as confirmed by concurrent use of the autoradiographic 2-14C-DG method. Underestimation of rCMRglc by 18F-FDG in normoglycemic conditions may be due to partial-volume effects. Computation of rCMRglc from 18F-FDG data in hyperglycemic animals may require, however, alternative rate and lumped constants for 18F-FDG.
Key Words: small animal PET • mouse • 18F-FDG • anesthesia • cerebral glucose metabolism
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