Clinical significance of striatal DOPA decarboxylase activity in Parkinson's disease

J Nucl Med. 1996 Feb;37(2):216-22.

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 (K1M = 0.0400 and k2M = 0.0420). We applied these values to calculate striatal DDC activity using the FDOPA compartmental model. We estimated k3D in this group using dynamic FDOPA-PET and population mean K1M and k2M values. We then applied the mean population K1M and k2M values to estimate k3D(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 (KiFD) 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, KiFD and SOR provided better between-group discrimination than did estimates of striatal DDC activity. KiFD and k3D(pop) both correlated significantly with quantitative disease severity ratings, with a similar degree of accuracy (r = 0.69 and 0.63 for k3D(pop) and KiFD, 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 KiFD is superior to k3D measurements for most clinical and research applications.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / diagnostic imaging
  • Brain / enzymology
  • Case-Control Studies
  • Corpus Striatum / enzymology*
  • Dihydroxyphenylalanine / analogs & derivatives*
  • Dihydroxyphenylalanine / pharmacokinetics
  • Dopa Decarboxylase / metabolism*
  • Female
  • Fluorine Radioisotopes*
  • Humans
  • Image Processing, Computer-Assisted
  • Male
  • Middle Aged
  • Models, Biological
  • Parkinson Disease / diagnostic imaging*
  • Parkinson Disease / enzymology*
  • Tomography, Emission-Computed / methods*

Substances

  • Fluorine Radioisotopes
  • 3-O-methyl-6-fluoro-dopa
  • fluorodopa F 18
  • Dihydroxyphenylalanine
  • Dopa Decarboxylase