Synthesis, radiolabeling and preliminary in vivo evaluation of [18F]FE-PE2I, a new probe for the dopamine transporter

Bioorg Med Chem Lett. 2009 Aug 15;19(16):4843-5. doi: 10.1016/j.bmcl.2009.06.032. Epub 2009 Jun 13.

Abstract

A new dopamine transporter (DAT) ligand, (E)-N-(3-iodoprop-2-enyl)-2beta-carbofluoroethoxy-3beta-(4'-methyl-phenyl) nortropane (FE-PE2I, 6), derived from PE2I (1), was prepared and found to be a potent inhibitor of rodent DAT in vitro. Compound 6 was radiolabelled with fluorine-18 (t(1/2)=109.8 min) for PET studies in monkeys. In vivo PET measurements showed a regional distribution in brain that corresponds to the known distribution of DAT. This binding was specific, reversible and the kinetics of [(18)F]6 binding in brain were faster than for its lead compound, [(11)C]1. The possible presence of a hydroxymethyl-radiometabolite formed by oxidation in the 3beta-benzylic position of [(18)F]6 warrants further detailed evaluation of the metabolism of [(18)F]6. [(18)F]6 is a potential radioligand for imaging DATs in the human brain with PET.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Dopamine Plasma Membrane Transport Proteins / antagonists & inhibitors
  • Dopamine Plasma Membrane Transport Proteins / metabolism*
  • Fluorine Radioisotopes / chemistry
  • Haplorhini
  • Humans
  • Isotope Labeling
  • Kinetics
  • Nortropanes / chemical synthesis*
  • Nortropanes / chemistry
  • Nortropanes / pharmacology
  • Positron-Emission Tomography
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / pharmacology
  • Rats

Substances

  • (E)-N-(3-iodoprop-2-enyl)-2beta-carbofluoroethoxy-3beta-(4'-methyl-phenyl) nortropane
  • Dopamine Plasma Membrane Transport Proteins
  • Fluorine Radioisotopes
  • Nortropanes
  • Radiopharmaceuticals