PET studies of peripheral catechol-O-methyltransferase in non-human primates using [18F]Ro41-0960

J Neural Transm (Vienna). 1998;105(10-12):1199-211. doi: 10.1007/s007020050123.

Abstract

We previously reported the results of PET (positron emission tomography) studies of [18F]Ro41-0960, a potent COMT inhibitor, in baboon brain. Here we report an evaluation of the pharmacokinetics and specificity of binding of [18F]Ro41-0960 in the peripheral organs of baboon. We observed a rapid clearance of the tracer from the heart and no significant uptake in the lung. In contrast, there was a high uptake and slow clearance in both kidney and liver, consistent with a high level of COMT in these peripheral organs. We also observed a dose-dependent inhibition of [18F]Ro41-0960 uptake by unlabeled Ro41-0960 (ED50 was 0.5 mg/kg in liver, and <0.01 mg/kg in kidney), with a halftime for recovery of COMT of about 25 h at the dose of 2 mg/kg of unlabeled Ro41-0960. This indicates a reversible tight binding interaction between COMT and Ro41-0960 in both liver and kidney and suggests that [18F]Ro41-0960 may be a useful radiotracer for future examination of the functional activity of COMT in the human body.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Benzophenones / metabolism*
  • Benzophenones / pharmacokinetics
  • Catechol O-Methyltransferase / metabolism*
  • Catechol O-Methyltransferase Inhibitors
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / metabolism*
  • Enzyme Inhibitors / pharmacokinetics
  • Female
  • Fluorine Radioisotopes
  • Kidney / metabolism
  • Liver / metabolism
  • Lung / metabolism
  • Metabolic Clearance Rate
  • Myocardium / metabolism
  • Organ Specificity
  • Papio
  • Tomography, Emission-Computed*

Substances

  • Benzophenones
  • Catechol O-Methyltransferase Inhibitors
  • Enzyme Inhibitors
  • Fluorine Radioisotopes
  • Ro 41-0960
  • Catechol O-Methyltransferase