title: Nigrostriatal function in humans studied with positron emission tomography.
abstract: The dopamine depletion that is characteristic of Parkinson's disease has been hypothesized to result from the combination of environmentally induced subclinical damage to the substantia nigra and the age-related loss of additional nigral neurons. Essential to this hypothesis is the existence of deteriorating function in the nigrostriatal pathway with advancing age. The present study was undertaken with [18F]6-fluoro-L-dopa and positron emission tomography to determine in vivo the effects of age on the nigrostriatal pathway in a series of 10 asymptomatic subjects (age range, 22-80 years; mean, 49.8 years). A graphical approach was used in the analysis of multiple-time tracer-uptake data to establish the presence of a compartment with unidirectional uptake and to calculate the rate constant, K, for uptake of [18F]6-fluoro-L-dopa from blood to striatum during steady-state, an index of the functional integrity of nigrostriatal nerve endings. There was a significant linear relationship between K and age (r = 0.80, p less than 0.005) with a decrease of 53.3% over the age range studied. These results demonstrate the application of a unidirectional transfer model to the analysis of [18F]6-fluoro-L-dopa and positron emission tomography data and provide in vivo confirmation of an age-related impairment of nigrostriatal function.
authors.affiliation: Division of Neurology, University of British Columbia, Vancouver, Canada.
authors.forename: W R
authors.initials: WR
authors.lastname: Martin
authors.forename: M R
authors.initials: MR
authors.lastname: Palmer
authors.forename: C S
authors.initials: CS
authors.lastname: Patlak
authors.forename: D B
authors.initials: DB
authors.lastname: Calne
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000502:physiology; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013378:Substantia Nigra / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000502:physiology; D014055:Tomography, Emission-Computed
chemical_list: C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine