No Dopamine Agonist Modulation of Brain [18F]FEOBV Binding in Parkinson's Disease

Mol Pharm. 2022 Apr 4;19(4):1176-1182. doi: 10.1021/acs.molpharmaceut.1c00961. Epub 2022 Mar 15.

Abstract

The [18F]fluoroethoxybenzovesamicol ([18F]FEOBV) positron emission tomography (PET) ligand targets the vesicular acetylcholine transporter. Recent [18F]FEOBV PET rodent studies suggest that regional brain [18F]FEOBV binding may be modulated by dopamine D2-like receptor agents. We examined associations of regional brain [18F]FEOBV PET binding in Parkinson's disease (PD) subjects without versus with dopamine D2-like receptor agonist drug treatment. PD subjects (n = 108; 84 males, 24 females; mean age 68.0 ± 7.6 [SD] years), mean disease duration of 6.0 ± 4.0 years, and mean Movement Disorder Society-revised Unified PD Rating Scale III 35.5 ± 14.2 completed [18F]FEOBV brain PET imaging. Thirty-eight subjects were taking dopamine D2-like agonists. Vesicular monoamine transporter type 2 [11C]dihydrotetrabenazine (DTBZ) PET was available in a subset of 54 patients. Subjects on dopamine D2-like agonists were younger, had a longer duration of disease, and were taking a higher levodopa equivalent dose (LED) compared to subjects not taking dopamine agonists. A group comparison between subjects with versus without dopamine D2-like agonist use did not yield significant differences in cortical, striatal, thalamic, or cerebellar gray matter [18F]FEOBV binding. Confounder analysis using age, duration of disease, LED, and striatal [11C]DTBZ binding also failed to show significant regional [18F]FEOBV binding differences between these two groups. Chronic D2-like dopamine agonist use in PD subjects is not associated with significant alterations of regional brain [18F]FEOBV binding.

Keywords: D2 receptor; acetylcholine; dopamine; fluoroethoxybenzovesamicol; positron emission tomography; striatum; vesicular acetylcholine transporter.

MeSH terms

  • Aged
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Dopamine Agonists* / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Parkinson Disease* / diagnostic imaging
  • Parkinson Disease* / drug therapy
  • Parkinson Disease* / metabolism
  • Positron-Emission Tomography / methods
  • Vesicular Acetylcholine Transport Proteins / metabolism

Substances

  • Dopamine Agonists
  • Vesicular Acetylcholine Transport Proteins