title: Occupancy of α7 Nicotinic Acetylcholine Receptors in the Brain by Tropisetron: A Positron Emission Tomography Study Using [(11)C]CHIBA-1001 in Healthy Human Subjects.
abstract: OBJECTIVE
  Agonists of α7-nicotinic acetylcholine receptors (nAChRs) have been developed as potential therapeutic drugs for neuropsychiatric diseases such as schizophrenia and Alzheimer's disease. Positron emission tomography (PET) is a noninvasive brain imaging technique to measure receptor occupancy in the living human brain. Although much effort has been expended to create specific PET radioligands for α7-nAChRs in the brain, only 4-[(11)C]methylphenyl-1,4-diazabicyclo[3.2.2.]nonane-4-carboxylate ([(11)C]CHIBA-1001) is currently available for clinical studies. In contrast, two 5-hydroxytryptamine-3 (5-HT(3)) receptor antagonists, tropisetron and ondansetron, have been used to treat patients with chemotherapy-induced or postoperative nausea and vomiting. Furthermore, tropisetron, but not ondansetron, possesses high affinity for α7-nAChRs. In the present study, we evaluated the receptor occupancy in the human brain after a single oral administration of tropisetron and ondansetron using [(11)C]CHIBA-1001 and PET.
  
  
  METHODS
  Two serial dynamic PET scans using [(11)C]CHIBA-1001 in healthy non-smoking male subjects were performed before and after receiving an oral administration of these medications.
  
  
  RESULTS
  A single oral administration of tropisetron, but not ondansetron, decreased the total distribution volume of [(11)C]CHIBA-1001 in the human brain.
  
  
  CONCLUSIONS
  This study shows that tropisetron, but not ondansetron, could bind to α7-nAChRs in the human brain after a single oral administration. Therefore, [(11)C]CHIBA-1001 may be a useful PET radioligand to measure the occupancy of α7-nAChRs in the human brain.
authors: Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.
authors: Masatomo
authors: M
authors: Ishikawa
authors: Muneyuki
authors: M
authors: Sakata
authors: Jun
authors: J
authors: Toyohara
authors: Keiichi
authors: K
authors: Oda
authors: Kenji
authors: K
authors: Ishii
authors: Jin
authors: J
authors: Wu
authors: Taisuke
authors: T
authors: Yoshida
authors: Masaomi
authors: M
authors: Iyo
authors: Kiichi
authors: K
authors: Ishiwata
authors: Kenji
authors: K
authors: Hashimoto
keywords: Ondansetron; Positron-emission tomography; Tropisetron; [C]CHIBA-1001; α7-nicotinic acetylcholine receptor