title: Evaluation of serotonin-2A receptor occupancy with 123I-5-I-R91150 and single-photon emission tomography before and after low-dose pipamperone administration in the canine brain.
abstract: OBJECTIVE
  To conduct a cost-efficient pilot study on the effect of low-dose pipamperone on the serotonin-2A receptor binding in a large animal model with conventional single-photon emission tomography modalities.
  
  
  METHODS
  Three healthy drug-naive female Beagle dogs were scanned before and after administration of a single-dose pipamperone of 5 and 10 mg. Acquisition was performed under general anesthesia 90 min after injection of the specific radioligand 123I-5-I-R91150 with a triple head gamma-camera (Triad, Trionix). Binding index and receptor occupancy were calculated on the emission data after image fusion with the emission data from the individual 99mTc-ethyl cysteinate dimer perfusion scans to optimize frontal cortex delineation.
  
  
  RESULTS
  A dose-dependent reduction of the binding index was observed after single low-dose pipamperone, suggestive for competition of this cold compound with the radioligand for the 5-HT2A receptor. The calculated mean-binding serotonin-2A binding index in the frontal cortex was 1.47 before treatment and reduced to 1.28 after one dose of pipamperone 5 mg and to 1.08 after one dose of pipamperone 10 mg. The calculated occupancy was 40.4% after one dose of 5 mg pipamperone and 83% after one dose of 10 mg pipamperone.
  
  
  CONCLUSIONS
  This experiment supports the hypothesis that pipamperone, even in the low-dose range, significantly blocks serotonin-2A receptors. This study also demonstrates the value of the canine model to investigate the effects of drugs on neurotransmitter systems. Repeated nuclear imaging brain scanning experiments with different paradigms and medication doses are possible with conventional imaging equipment in a well-accepted laboratory species.
authors.affiliation: Medical Imaging Department, Faculty of Veterinary Medicine, Laboratory of Radiopharmacy, Ghent University, Ghent, Belgium. kathelijne.peremans@ugent.be
authors.forename: Kathelijne
authors.initials: K
authors.lastname: Peremans
authors.forename: Bart
authors.initials: B
authors.lastname: De Spiegeleer
authors.forename: Erik
authors.initials: E
authors.lastname: Buntinx
authors.forename: Andre
authors.initials: A
authors.lastname: Dobbeleir
authors.forename: Simon
authors.initials: S
authors.lastname: Vermeire
authors.forename: Eva
authors.initials: E
authors.lastname: Vandermeulen
authors.forename: Filip
authors.initials: F
authors.lastname: De Vos
authors.forename: Anton
authors.initials: A
authors.lastname: Megens
authors.forename: Jos
authors.initials: J
authors.lastname: Eersels
authors.forename: Kurt
authors.initials: K
authors.lastname: Audenaert