Adenosine A1 receptors measured with 11 C-MPDX PET in early Parkinson's disease

Synapse. 2017 Aug;71(8). doi: 10.1002/syn.21979. Epub 2017 Apr 25.

Abstract

Adenosine A1 receptors (A1 Rs) interact negatively with dopamine D1 receptors (D1 Rs) in neurons of the basal ganglia's direct pathway, while adenosine A2A receptors (A2A Rs) negatively interact with dopamine D2 receptors (D2 Rs) in indirect-pathway neurons. The aim of this study was to investigate the cerebral density of A1 Rs in Parkinson's disease (PD) in its early stages, using PET scans with the radioligand 8-dicyclopropylmethyl-1-11 C-methyl-3-propylxanthine (11 C-MPDX). We studied 10 drug-naïve patients with early PD. Each patient was also examined for dopamine transporters (DATs) and D2 Rs by PET using 11 C-2-β-carbomethoxy-3-β-(4-fluorophenyl)-tropane (11 C-CFT) and 11 C-raclopride (11 C-RAC), respectively. Ten elderly, healthy volunteers were recruited as controls for 11 C-MPDX PET scanning and eight elderly volunteers were recruited as controls for 11 C-CFT and 11 C-RAC PET scanning. The PET scans revealed a decrease in the uptake ratio index (URI) of 11 C-CFT and an increase in the URI of 11 C-RAC in patients. In the temporal lobe, the binding potential for 11 C-MPDX was higher in the patient group than in healthy subjects, but not in the other regions examined, including the striatum. In patients, we observed motor-symptom asymmetry and a relationship between parkinsonism and the striatal density of DATs, but not A1 R density. In the putamen of early PD, asymmetrical down-regulation of A2A Rs is likely a compensatory mechanism in response to a decrease in dopamine. However, our study suggests that A1 Rs are unaltered in the putamen of early PD.

Keywords: dopamine; positron emission tomography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Brain Mapping
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Parkinson Disease / diagnostic imaging*
  • Parkinson Disease / metabolism*
  • Positron-Emission Tomography*
  • Raclopride
  • Radiopharmaceuticals*
  • Receptor, Adenosine A1 / metabolism*
  • Receptors, Dopamine D2 / metabolism
  • Tropanes
  • Xanthines*

Substances

  • 1-methyl-8-dicyclopropylmethyl-1-methyl-3-propylxanthine
  • 2beta-carbomethoxy-3beta-(4-(11C)fluorophenyl)tropane
  • DRD2 protein, human
  • Dopamine Plasma Membrane Transport Proteins
  • Radiopharmaceuticals
  • Receptor, Adenosine A1
  • Receptors, Dopamine D2
  • Tropanes
  • Xanthines
  • Raclopride