[123I]FP-CIT binds to the dopamine transporter as assessed by biodistribution studies in rats and SPECT studies in MPTP-lesioned monkeys

Synapse. 1997 Nov;27(3):183-90. doi: 10.1002/(SICI)1098-2396(199711)27:3<183::AID-SYN4>3.0.CO;2-9.

Abstract

[123I]FP-CIT (N-omega-fluoropropyl-2 beta-carbomethoxy-3 beta-(4-iodophenyl)-tropane), a radioiodinated cocaine analogue, was evaluated as an agent for the in vivo labeling of dopamine (DA) transporters by biodistribution studies in rats and by single photon emission computed tomography (SPECT) studies in unilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys. In rats, intravenous injection of [123I]FP-CIT resulted in high accumulation of radioactivity in the striatum. Less pronounced uptake was seen in brain areas with high densities of serotonergic uptake sites. While striatal uptake of radioactivity after injection of [123I]FP-CIT was displaced significantly by GBR12,909 but not by fluvoxamine, the opposite was observed in brain areas known to be rich of serotonin transporters. Monkeys which were unilaterally treated with neurotoxic doses of MPTP showed severe loss of striatal [123I]FP-CIT uptake at the side of treatment. The results of this study indicate that [123I]FP-CIT, although not being a selective radioligand, binds specifically to the striatal DA transporter in vivo and thus suggest that [123I]FP-CIT promises to be a suitable radioligand for SPECT imaging of DA transporters in humans.

MeSH terms

  • Animals
  • Binding, Competitive / drug effects
  • Brain / drug effects
  • Brain / metabolism
  • Carrier Proteins / metabolism*
  • Dopamine Agents / toxicity*
  • Dopamine Plasma Membrane Transport Proteins
  • Iodine Radioisotopes
  • MPTP Poisoning*
  • Male
  • Membrane Glycoproteins*
  • Membrane Transport Proteins*
  • Neostriatum / drug effects
  • Neostriatum / metabolism
  • Nerve Tissue Proteins / metabolism*
  • Protein Binding
  • Radioligand Assay
  • Rats
  • Rats, Wistar
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon
  • Tropanes / metabolism*
  • Tropanes / pharmacokinetics

Substances

  • Carrier Proteins
  • Dopamine Agents
  • Dopamine Plasma Membrane Transport Proteins
  • Iodine Radioisotopes
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Tropanes
  • 2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane