Increased Binding Potential of Brain Adenosine A1 Receptor in Chronic Stages of Patients with Diffuse Axonal Injury Measured with [1-methyl-11C] 8-dicyclopropylmethyl-1-methyl-3-propylxanthine Positron Emission Tomography Imaging.

The positron emission tomography (PET) radioligand for adenosine A1 receptor (A1R) [1-methyl-11C] 8-dicyclopropylmethyl-1-methyl-3-propylxanthine (MPDX) has recently been developed for human brain imaging. In the present study, we evaluated the alteration of the A1R in patients with diffuse axonal injury (DAI) in chronic stage in vivo. Ten patients with DAI (7 men and 3 women) were included in this study. Three PET examinations were sequentially performed to measure A1R binding with 11C-MPDX, glucose metabolism with 18F-fluorodeoxyglucose (FDG), and central benzodiazepine receptor binding with 11C-flumazenil (FMZ), and decreases of 11C-FMZ uptake indicate neuronal loss. 11C- MPDX did not depict any lesion with significantly decreased nondisplaceable binding potential (BPND) in comparison to healthy controls (14 men) in region of interest (ROI) analysis. Instead, it showed a significant increase of BPND in the lower frontal and posterior cingulate cortexes and rolandic area (p < 0.05) in ROI analysis. In 18F-FDG PET, the standardized uptake values (SUVs) ratio to the whole brain were decreased in anterior and posterior cingulate gyrus compared to controls (14 men and 9 women; p < 0.01). In 11C-FMZ PET, the SUV ratio to the cerebellum was decreased in anterior cingulate gyrus in ROI analysis (controls, 9 men and 6 women; p < 0.01). The area with significantly increased 11C-MPDX binding, lower frontal cortex, rolandic area, and posterior cingulate gyrus, did not overlap with the areas of neuronal loss detected by decreased 11C-FMZ binding and did not completely overlap with area of reduced18F-FDG uptake. We obtained the first 11C-MPDX PET images reflecting the A1R BPND in human DAI brain in vivo. 11C-MPDX depicted increased A1R BPND in the areas surrounding the injured brain, whereas 18F-FDG demonstrated reduction throughout the brain. The results suggested that A1R might continuously confer neuroprotective or neuromodulatory effects in DAI even in the chronic stage.

Citation

Shihori Hayashi, Motoki Inaji, Tadashi Nariai, Keiichi Oda, Muneyuki Sakata, Jun Toyohara, Kenji Ishii, Kiichi Ishiwata, Taketoshi Maehara. Increased Binding Potential of Brain Adenosine A1 Receptor in Chronic Stages of Patients with Diffuse Axonal Injury Measured with [1-methyl-11C] 8-dicyclopropylmethyl-1-methyl-3-propylxanthine Positron Emission Tomography Imaging. Journal of neurotrauma. 2017 Nov 03

PMID: 28728462

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