Three-dimensional measurement of glucose uptake and usage in vivo provides a valuable indicator of the metabolic state and activity in the brain, heart, muscle, and other tissues. PET imaging using a sugar molecule labeled with the positron emitting radionucleotide, 18F-fluorodeoxyglucose (FDG) reveals cellular uptake of glucose from the blood. FDG is used in preclinical as well as clinical imaging, notably in screening for cancer metastasis.
FDG is often created in the morning for use by mid- to late-day, due to the short half-life of 18F (110 minutes). Any circadian cycle in tissue glucose uptake would affect PET results depending on the time of day the scan is taken.
Prior studies using 2-deoxy-D[14C]-glucose (2DG) to trace glucose usage have shown only a few brain areas with clear 24-hour rhythms. The 2DG method provides precisely localized quantitation of glucose use at one time point per animal. However, it cannot reveal patterns in glucose uptake across the whole body within individuals over time.
To examine the question of circadian cycling, Van der Veen and colleagues used a Bruker Albira imaging system to create fused CT images (voxel size 250 Hounsfield units) and PET scans (voxel size 0.6560.6560.944 mm [xyz]) of FDG in the hearts and brains of living mice across the 24-hour light/dark cycle.
The FDG localized strongly to both heart and brain. The heart data did not show any regular temporal pattern in glucose use, though variations within mice were common through the day/night cycle. The whole brain showed a strong daily rhythm in glucose update. Brain glucose uptake peaked – reaching about 150% of average levels – at mid-dark in the light/dark cycle, the most active time of day for these nocturnal animals.
Data from specific brain regions, identified using a PET-specific mouse brain template, showed circadian cycling of glucose uptake in most brain regions examined. Rhythms of above-average amplitude appeared in the olfactory bulb and cortex, while cycling of below-average amplitude was evident in the amygdala, brain stem and hypothalamus. The authors propose that low-amplitude cycles could reflect multiple rhythms in the same brain structure, sufficiently out-of-phase to dampen the summed amplitude for the region.
The FDG method on the Albira imaging system revealed greater and more complex variations in brain glucose uptake than prior studies with 2DG suggested for glucose utilization. As the authors note, the results point to a need to account for time of day in both preclinical and clinical studies of brain glucose uptake.
Van der Veen DR, Shao J, Chapman S, Leevy WM, Duffield GE. A 24-hour temporal profile of in vivo brain and heart pet imaging reveals a nocturnal peak in brain 18F-fluorodeoxyglucose uptake. PLoS One 2012;7: e31792. PubMed Central: PMC3285174.