Abstract
BackgroundWe studied the distribution and expression of translocator protein in the human brain using 11C-[R]-PK-11195 positron emission tomography (PK11195 PET) and evaluated age-related changes.MethodsA dynamic PK11195 PET scan was performed in 15 normal healthy adults (mean age: 29 ±8.5 years (range: 20 to 49); 7 males) and 10 children (mean age: 8.8 ±5.2 years (range: 1.2 to 17); 5 males), who were studied for potential neuroinflammation but showed no focally increased PK11195 binding. The PET images were evaluated by calculating standard uptake values and regional binding potential, based on a simplified reference region model, as well as with a voxel-wise analysis using statistical parametric mapping.ResultsPK11195 uptake in the brain is relatively low, compared with the subcortical structures, and symmetrical. The overall pattern of PK11195 distribution in the brain does not change with age. PK11195 uptake was lowest in the frontal-parietal-temporal cortex and highest in the pituitary gland, midbrain, thalamus, basal ganglia, occipital cortex, hippocampus and cerebellum, in descending order. White matter showed negligible PK11195 uptake. Overall, brain PK11195 uptake increased with age, with midbrain and thalamus showing relatively higher increases with age compared with other brain regions.ConclusionsThe brain shows low PK11195 uptake, which is lower in the cortex and cerebellum compared with subcortical structures, suggesting a low level of translocator protein expression. There is no hemispheric asymmetry in PK11195 uptake and the overall pattern of PK11195 distribution in the brain does not change with age. However, brain PK11195 uptake increases with age, with the thalamus and midbrain showing relatively higher increases compared with other brain regions. This increase in uptake suggests an age-related increase in translocator protein expression or the number of cells expressing these receptors or both.
Highlights
We studied the distribution and expression of translocator protein in the human brain using 11C-[R]PK-11195 positron emission tomography (PK11195 PET) and evaluated age-related changes
Voxel-wise analysis Voxel-wise analysis of SUV images was performed to assess the global differences in PK11195 uptake between adults (≥18 years of age; n = 15) and children (6 to 18 years of age; n = 8), as we have previously shown the feasibility of statistical parametric mapping (SPM) analysis using an adult template [14]
Overall PK11195 uptake increased with age, with the thalamus and midbrain showing relatively higher increases compared with other brain regions
Summary
We studied the distribution and expression of translocator protein in the human brain using 11C-[R]PK-11195 positron emission tomography (PK11195 PET) and evaluated age-related changes. The carbon-11 labeled positron emission tomography (PET) tracer 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)3-isoquinoline carboxamide (11C-[R]-PK-11195 (PK11195)) selectively binds to TSPOs and has been used most for in vivo imaging of neuroinflammation [9]. Experience with this tracer in children is very limited, and detailed PK11195 brain PET kinetics and data about age-related changes are lacking. Emission data were acquired in threedimensional mode and measured attenuation correction as well as scatter and decay correction were applied to all PET images. Eight children required sedation, which was performed using intravenous nembutal (3 mg/kg), as it has been reported that acute short-term use of barbiturate does not affect TSPO receptors [11]
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