Potential of [(18)F]beta-CFT-FE (2beta-carbomethoxy-3beta-(4-fluorophenyl)-8-(2-[(18)F]fluoroethyl)nortropane) as a dopamine transporter ligand: A PET study in the conscious monkey brain

Synapse. 2004 Oct;54(1):37-45. doi: 10.1002/syn.20059.

Abstract

A dopamine transporter (DAT) ligand 2beta-carbomethoxy-3beta-(4-fluoro-phenyl)-8-(2-[(18)F]fluoroethyl)nortropane ([(18)F]beta-CFT-FE) was synthesized and evaluated in comparison with [(11)C]beta-CFT in monkey brain using animal positron emission tomography (PET). [(18)F]beta-CFT-FE and [(11)C]beta-CFT were injected intravenously to conscious monkeys for a 91-min PET scan with arterial blood sampling for metabolite analysis. In the conscious state, [(18)F]beta-CFT-FE provided a peak about 20 min after the injection and declined thereafter in the striatum of monkey brain, while [(11)C]beta-CFT continuously increased with time up to 91 min after injection. Metabolite analysis revealed that [(18)F]beta-CFT-FE was more rapidly metabolized in plasma than [(11)C]beta-CFT. The striatal binding of both ligands was dose-dependently displaced by preadministration of a specific DAT inhibitor, GBR12909, at doses of 0.5 and 5 mg/kg; however, the displacement degree of [(11)C]beta-CFT-FE was higher than that of [(18)F]beta-CFT. The effects of the anesthetics, ketamine and isoflurane, on binding were more prominent in [(11)C]beta-CFT than [(18)F]beta-CFT-FE. Specificity and affinity of beta-CFT-FE to DAT were evaluated in an in vitro assay using cloned human DAT, serotonin transporter, and norepinephrine transporter in comparison with other conventional DAT ligands, showing that beta-CFT-FE had lower affinity and higher specificity to DAT than beta-CFT and beta-CIT. These results suggested that [(18)F]beta-CFT-FE could be a potential imaging agent for DAT, providing excellent selectivity and tracer kinetics for quantitative PET imaging.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics
  • Animals
  • Brain / drug effects
  • Brain / metabolism*
  • Carbon Radioisotopes / blood
  • Carbon Radioisotopes / pharmacokinetics
  • Consciousness
  • Dopamine Plasma Membrane Transport Proteins
  • Dopamine Uptake Inhibitors / pharmacology
  • Dose-Response Relationship, Drug
  • Fluorine Radioisotopes / blood
  • Fluorine Radioisotopes / pharmacokinetics*
  • Humans
  • Isoflurane / pharmacology
  • Ketamine / pharmacology
  • Ligands
  • Macaca mulatta
  • Membrane Glycoproteins / metabolism*
  • Membrane Transport Proteins / metabolism*
  • Nerve Tissue Proteins / metabolism*
  • Nortropanes / blood
  • Nortropanes / pharmacokinetics*
  • Piperazines / pharmacology
  • Sensitivity and Specificity
  • Tomography, Emission-Computed

Substances

  • Anesthetics
  • Carbon Radioisotopes
  • Dopamine Plasma Membrane Transport Proteins
  • Dopamine Uptake Inhibitors
  • Fluorine Radioisotopes
  • Ligands
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Nortropanes
  • Piperazines
  • SLC6A3 protein, human
  • Ketamine
  • vanoxerine
  • Isoflurane