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 ¹⁸F-FDG and a small animal PET scanner. rCMR _glc determined with ¹⁸F-FDG PET was compared with values determined simultaneously by the autoradiographic 2-¹⁴C-DG method. In addition, we compared the rCMR_glc 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. rCMR_glc 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 rCMR_glc 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 rCMR_glc values with ¹⁸F-FDG PET were higher (by 17.3%) than those with 2- ¹⁴C-DG. Values for rCMR_glc 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 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 ¹⁸F-FDG and glucose uptake to the brain under hyperglycemia. Conclusion: We were able to obtain accurate absolute quantification of rCMR_glc with mouse ¹⁸F-FDG PET imaging as confirmed by concurrent use of the autoradiographic 2-¹⁴C-DG method. Underestimation of rCMR _glc by ¹⁸F-FDG in normoglycemic conditions may be due to partial-volume effects. Computation of rCMR_glc from ¹⁸F-FDG data in hyperglycemic animals may require, however, alternative rate and lumped constants for ¹⁸F-FDG.