[(11)C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain

Eur J Nucl Med Mol Imaging. 2003 Sep;30(9):1220-30. doi: 10.1007/s00259-003-1212-3. Epub 2003 Jun 13.


The aim of this study was to explore the potential of a new selective dopamine transporter (DAT) compound as a radioligand for positron emission tomography (PET) examination of DAT in the human brain. The high affinity DAT compound N-(3-iodoprop-2 E-enyl)-2beta-carbomethoxy-3beta-(4-methylphenyl)nortropane (PE2I) was radiolabelled by the O-methylation approach and the binding was characterised by PET in cynomolgus monkeys and a healthy man. Metabolite levels in plasma were measured by gradient high-performance liquid chromatography. O-methylation of the corresponding free acid precursor with [(11)C]methyl triflate gave high radiochemical yield (80%) and specific radioactivity (55 GBq/ microM). [(11)C]PE2I binding in cynomolgus monkeys was nine times higher in the striatum than in the cerebellum at peak equilibrium, which appeared 55-65 min after injection. Displacement and pretreatment measurements using unlabelled beta-CIT, GBR 12909, cocaine, citalopram and maprotiline confirmed that [(11)C]PE2I binds selectively to DAT. In a preliminary study in one human subject the radioactivity ratios of the striatum and substantia nigra to the cerebellum were 10 and 1.8, respectively, at peak equilibrium, which appeared at 40-50 min and 20 min, respectively, after injection. The fraction of the total radioactivity in monkey and human plasma representing unchanged [(11)C]PE2I was 15-20% at 40 min after injection. The present characterisation of binding in monkey and man suggests that [(11)C]PE2I is a suitable PET radioligand for quantitative regional examination of DAT in man.

Publication types

  • Case Reports
  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Animals
  • Brain / diagnostic imaging*
  • Brain / metabolism*
  • Dopamine Plasma Membrane Transport Proteins
  • Humans
  • Macaca fascicularis
  • Male
  • Membrane Glycoproteins*
  • Membrane Transport Proteins / metabolism*
  • Metabolic Clearance Rate
  • Nerve Tissue Proteins / metabolism*
  • Nortropanes / pharmacokinetics*
  • Radiopharmaceuticals / blood
  • Radiopharmaceuticals / pharmacokinetics
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tissue Distribution
  • Tomography, Emission-Computed / methods*


  • Dopamine Plasma Membrane Transport Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • N-(3-iodoprop-2-enyl)-2-beta-carbomethoxy-3-(4-methylphenyl)nortropane
  • Nerve Tissue Proteins
  • Nortropanes
  • Radiopharmaceuticals
  • SLC6A3 protein, human