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Clinical Significance of Striatal DOPA Decarboxylase Activity in Parkinson's Disease

The Departments of Neurology, Research, Medicine and Biostatistics, North Shore University Hospital/Cornell University Medical College, Manhasset, New York

Correspondence: For correspondence or reprints contact: David Eidelberg, MD, Department of Neurology. North Shore University Hospital/Cornell University Medical College, 300 Community Dr., Manhasset, NY 11030.

ABSTRACT

We performed dynamic PET studies with fluorodopa (FDOPA) in 9 normal volunteers and 16 patients with Parkinson's disease to investigate the applicability of dopa decarboxylase (DDC) activity measurements as useful markers of the parkinsonian disease process. Methods: From the 3-O-methyl-FDOPA (3OMFD)/PET studies, we obtained mean population values of the kinetic rate constants for 3OMFD (K₁^M = 0.0400 and k₂^M 0.0420). We applied these values to calculate striatal DDC activity using the FDOPA compartmental model. We estimated k₃^D in this group using dynamic FDOPA-PET and population mean K₁^M and K₂^M values. We then applied the mean population K₁^M and K₂^M values to estimate k₃^D (pop) to a new group (6 normal volunteers and 11 patients) studied only with dynamic FDOPA-PET. In all FDOPA/PET studies, we calculated striatal uptake rate constants(K₁^FD) using a graphical method and also measured the striato-occipital ratio (SOR). Results: Although DDC activity has been postulated as a precise indicator of presynaptic nigrostriatal dopaminergic function, K₁^FD and SOR provided better between-group discrimination than did estimates of striatal DDC activity. K₁^FD and k₃^D (pop) both correlated significantly with quantitative disease severity ratings, with a similar degree of accuracy (r = 0.69 and 0.63 for k₃^D (pop)and K₁^FD respectively; p < 0.01). Conclusion: Although estimated striatal DDC activity correlates with clinical disability, this measure is comparably less effective for early diagnosis. We conclude that a simple estimate such as striatal K₁^FD is superior to k₃^D measurements for most clinical and research applications.

Key Words: DOPA decarboxylase activity • PET • parkinsonism

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