Awake (18)F-FDG PET Imaging of Memantine-Induced Brain Activation and Test–Retest in Freely Running Mice

PET scans of the mouse brain are usually performed with anesthesia to immobilize the animal. However, it is desirable to avoid the confounding factor of anesthesia in mouse-brain response. Methods: We developed and validated brain PET imaging of awake, freely moving mice. Head-motion tracking was performed using radioactive point-source markers, and we used the tracking information for PET-image motion correction. Regional (18)F-FDG brain uptake in a test, retest, and memantine-challenge study was measured in awake (n = 8) and anesthetized (n = 8) C57BL/6 mice. An awake uptake period was considered for the anesthesia scans. Results: Awake (motion-corrected) PET images showed an (18)F-FDG uptake pattern comparable to the pattern of anesthetized mice. The test–retest variability (represented by the intraclass correlation coefficient) of the regional SUV quantification in the awake animals (0.424–0.555) was marginally lower than that in the anesthetized animals (intraclass correlation coefficient, 0.491–0.629) over the different regions. The increased memantine-induced (18)F-FDG uptake was more pronounced in awake (+63.6%) than in anesthetized (+24.2%) animals. Additional behavioral information, acquired for awake animals, showed increased motor activity on a memantine challenge (total distance traveled, 18.2 ± 5.28 m) compared with test–retest (6.49 ± 2.21 m). Conclusion: The present method enables brain PET imaging on awake mice, thereby avoiding the confounding effects of anesthesia on the PET reading. It allows the simultaneous measurement of behavioral information during PET acquisitions. The method does not require any additional hardware, and it can be deployed in typical high-throughput scan protocols.