In vivo positron emission tomographic evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson's disease

Ann Neurol. 2000 Apr;47(4):493-503.


Clinical symptoms of Parkinson's disease (PD) do not manifest until dopamine (DA) neuronal loss reaches a symptomatic threshold. To explore the mechanisms of functional compensation that occur in presynaptic DA nerve terminals in PD, we compared striatal positron emission tomographic (PET) measurements by using [11C]dihydrotetrabenazine ([11C]DTBZ; labeling the vesicular monoamine transporter type 2), [11C]methylphenidate (labeling the plasma membrane DA transporter), and [18F]dopa (reflecting synthesis and storage of DA). Three consecutive PET scans were performed in three-dimensional mode by using each tracer on 35 patients and 16 age-matched, normal controls. PET measurements by the three tracers were compared between subgroups of earlier and later stages of PD, between drug-naive and drug-treated subgroups of PD, and between subregions of the parkinsonian striatum. The quantitative relationships of [18F]dopa and [11]DTBZ, and of [11C]methylphenidate and [11C]DTBZ, were compared between the PD and the normal control subjects. We found that [18F]dopa Ki was reduced less than the binding potential (Bmax/Kd) for [11C]DTBZ in the parkinsonian striatum, whereas the [11C]methylphenidate binding potential was reduced more than [11C]DTBZ binding potential. These observations suggest that the activity of aromatic L-amino acid decarboxylase is up-regulated, whereas the plasma membrane DA transporter is down-regulated in the striatum of patients with PD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carbon Radioisotopes
  • Carrier Proteins / metabolism
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / metabolism
  • Dopamine / metabolism*
  • Dopamine Plasma Membrane Transport Proteins
  • Down-Regulation / physiology
  • Fluorine Radioisotopes
  • Homovanillic Acid / metabolism
  • Humans
  • Membrane Glycoproteins*
  • Membrane Transport Proteins*
  • Middle Aged
  • Nerve Tissue Proteins*
  • Parkinson Disease / diagnostic imaging*
  • Parkinson Disease / metabolism*
  • Presynaptic Terminals / metabolism*
  • Tetrabenazine / analogs & derivatives
  • Tomography, Emission-Computed*


  • Carbon Radioisotopes
  • Carrier Proteins
  • Dopamine Plasma Membrane Transport Proteins
  • Fluorine Radioisotopes
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • dihydrotetrabenazine
  • Dopamine
  • Homovanillic Acid
  • Tetrabenazine