Copyright 2005 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2005
Hilker et al1 have recently reported that the magnitude of the net influx of fluorodopa F 18 ([18F]fluorodopa) to the putamen calculated relative to the occipital cortex (Kinocc) declines exponentially with time after the onset of Parkinson disease. The authors conclude that disease onset precedes clinical diagnosis by 6 years, concurring with some earlier reports2,3 but with the novel implication that fulminant pathogenesis has reduced Kinocc by 50% during the relatively brief preclinical phase. However, we wish to propose an alternative interpretation of their findings based on principles of compartmental analysis. The macroparameter Kinocc used by Hilker and colleagues is equal to the magnitude of the net blood-brain clearance of [18F]fluorodopa (Kinapp; milliliters per gram per minute) divided by the [18F]fluorodopa distribution volume in the brain. The net clearance, Kinapp, is defined as the product of the unidirectional blood-brain clearance of [18F]fluorodopa (K1D) and the relative activity of dopa decarboxylase (k3D) divided by the sum of the rate constants for washout of [18F]fluorodopa back to circulation (k2D) and k3D. Assuming the magnitudes of K1D and k2D to be constant, the magnitude of Kinapp must have a hyperbolic relationship with k3D, which may be the more accurate indicator of dopamine loss since it reflects the cerebral activity of dopa decarboxylase rather than utilization of exogenous levodopa from blood. Indeed, we have found k3D to have a linear relationship with the number of dopamine neurons surviving in fetal mesencephalic grafts.4
Borghammer P, Kumakura Y, Cumming P. Fluorodopa F 18 Positron Emission Tomography and the Progression of Parkinson Disease. Arch Neurol. 2005;62(9):1480. doi:10.1001/archneur.62.9.1480-a
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