Biodistribution and displacement studies of the selective 5-HT2A receptor antagonist 123I-5-I-R91150 in the normal dog

Nucl Med Commun. 2002 Oct;23(10):1019-27. doi: 10.1097/00006231-200210000-00013.

Abstract

There is increasing interest in mapping receptors in vivo by using functional imaging modalities such as single photon emission tomography (SPET) and positron emission tomography (PET). Since SPET is a more accessible functional imaging modality than PET and, overall, it is more economical, radioligands suitable for this technique are in greater demand. Recently, 123I-5-I-R91150, a radioligand with high selectivity and affinity for 5-HT(2A) receptors in the brain, was introduced for SPET. This study reports on the whole-body distribution and brain uptake of the selective 123I-5-I-R91150 ligand in four normal dogs. The frontal to cerebellar ratio of uptake in time was determined in three dogs. Time-activity curve of venous blood was determined in one dog. Maximal global brain uptake was found at 10-60 min post-injection. Higher brain uptake was noted in the frontal cortical areas compared to the cerebellum. The frontal-cerebellar ratio reached the highest values at 90-180 min. Reversibility and pharmacological selectivity of ligand binding was demonstrated through displacement and blocking studies with the 5-HT(2A) receptor antagonist ketanserin. This study demonstrates that the specific 5-HT(2A) iodinated ligand can be used for imaging and semi-quantification of the 5-HT(2A) receptors in the canine brain in vivo by using SPET.

MeSH terms

  • Animals
  • Binding, Competitive / drug effects
  • Brain / diagnostic imaging
  • Dogs
  • Ketanserin / pharmacokinetics
  • Piperidines / chemical synthesis
  • Piperidines / pharmacokinetics*
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / pharmacokinetics*
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Serotonin / metabolism*
  • Serotonin Antagonists / chemical synthesis
  • Serotonin Antagonists / pharmacokinetics*
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon
  • Whole-Body Counting

Substances

  • Piperidines
  • R 91150
  • Radiopharmaceuticals
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Ketanserin