Synthesis and evaluation of 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-[11C]ethyl-1,3-dihydro-2H-benzimidazol-2-one as a brain ORL1 receptor imaging agent for positron emission tomography

Nucl Med Biol. 2003 Jan;30(1):51-9. doi: 10.1016/s0969-8051(02)00352-9.

Abstract

1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-[(11)C]ethyl-1,3-dihydro-2H-benzimidazol-2-one ([(11)C]CPEB) was synthesized by [(11)C]N-ethylation and evaluated as a potential brain ORL1 receptor imaging agent by positron emission tomography. The uptake of [(11)C]CPEB in the mouse brain was 1.9% dose/g, 2 min post-injection, and gradually decreased with time. Receptor-specific binding was observed, however, the contribution of other receptors was observed and the non-specific binding of [(11)C]CPEB was too high for imaging receptors in vivo. Therefore, [(11)C]CPEB is not a suitable tracer for in vivo ORL1 receptor imaging.

Publication types

  • Comparative Study
  • Evaluation Study

MeSH terms

  • Animals
  • Benzimidazoles / chemical synthesis*
  • Benzimidazoles / pharmacokinetics*
  • Brain / diagnostic imaging*
  • Brain / drug effects
  • Brain / metabolism*
  • Carbon Radioisotopes / chemistry
  • Carbon Radioisotopes / pharmacokinetics
  • Isotope Labeling / methods
  • Male
  • Metabolic Clearance Rate
  • Mice
  • Mice, Inbred Strains
  • Nociceptin
  • Nociceptin Receptor
  • Opioid Peptides / pharmacology
  • Organ Specificity
  • Piperidines / chemical synthesis*
  • Piperidines / pharmacokinetics*
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / pharmacokinetics
  • Receptors, Opioid / metabolism*
  • Reference Values
  • Tissue Distribution
  • Tomography, Emission-Computed / methods

Substances

  • Benzimidazoles
  • Carbon Radioisotopes
  • J 113397
  • Opioid Peptides
  • Piperidines
  • Radiopharmaceuticals
  • Receptors, Opioid
  • Nociceptin Receptor
  • Oprl1 protein, mouse