Improved sensitivity of human brain MAO B measurement using deuterium substituted [{sup 11}C]L-deprenyl ([{sup 11}C]L-deprenyl-D2)
- Brookhaven National Laboratory, Upton, NY (United States); and others
Post-mortem reports that human brain monoamine oxidase B (MAO B) increases in normal aging and neurodegenerative disorders due to the proliferation of MAO B-rich glial cells suggest that PET measures of MAO B may track gliosis. We have recently shown that the MAO B tracer [{sup 11}C]L-deprenyl has limited sensitivity in regions of high MAO B due to its rapid rate of trapping. This limits its utility for measuring MAO B in brain regions where MAO B is higher and/or where blood flow is low. We have recently demonstrated that [{sup 11}C]L-deprenyl-D2 has improved sensitivity in regions of high MAO B due to the deuterium isotope effect which reduces the rate of trapping. We report studies [{sup 11}C]L-deprenyl-D2 in normal human brain in 16 healthy men and women (age range 23-73) to assess tracer sensitivity, regional distribution, and reproducibility. Graphical analysis for irreversible systems was used to calculate Ki (influx constant) as an index of MAO B concentration in different brain regions. The uptake of carbon-11 in different brain regions was rapid, peaking at 5 minutes and plateauing from 30-60 minutes after an initial clearance. MAO B was highest in subcortical regions: thalamus{ge}basal ganglia>cingulate gyrus>frontal cortex=occipital cortex=cerebellum in agreement with post-mortem measurements. Ki values were highly correlated within an individual. Repeated measures at 1-4 week intervals were highly correlated (r=0.9; p=0.0001). In women (n=8: age range 23-73), Ki increased with increasing age for 8 brain regions (p < 0.04). Though men (N=8; age range 34-70) showed no correlation with age, a larger sample size is needed to adequately assess trends. In summary, the use of [{sup 11}C]L-deprenyl-D2 improves the measurement of MAO B in the human brain permitting its investigation as a positive tracer for glial cell proliferation in neurodegenerative disorders.
- OSTI ID:
- 441615
- Report Number(s):
- CONF-950603--
- Journal Information:
- Journal of Nuclear Medicine, Journal Name: Journal of Nuclear Medicine Journal Issue: Suppl.5 Vol. 36; ISSN JNMEAQ; ISSN 0161-5505
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BASIC STUDIES
AGE DEPENDENCE
AGING
AMINE OXIDASES
BLOOD FLOW
BRAIN
CARBON 11
CEREBELLUM
CLEARANCE
DIAGNOSTIC TECHNIQUES
ETIOLOGY
LABELLED COMPOUNDS
MEASURING METHODS
NERVOUS SYSTEM DISEASES
PATHOLOGICAL CHANGES
POSITRON COMPUTED TOMOGRAPHY
SENSITIVITY
THALAMUS
TRACER TECHNIQUES
UPTAKE