[11C]CHIBA-1001 as a Novel PET Ligand for α7 Nicotinic Receptors in the Brain: A PET Study in Conscious Monkeys
| Autor: | Makoto Takahagi, Masaaki Matsuo, Hiroyuki Ohba, Shingo Nishiyama, Masaomi Iyo, Takeru Kitashoji, Kenji Hashimoto, Hideo Tsukada, Tatsuhiko Kobashi |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Male
Consciousness alpha7 Nicotinic Acetylcholine Receptor medicine.drug_class Mental Health/Neuropsychiatric Disorders Science Phencyclidine Pharmacology Receptors Nicotinic complex mixtures medicine Radioligand Animals Receptor Mental Health/Schizophrenia and Other Psychoses Multidisciplinary Chemistry Brain Esters Human brain Ligand (biochemistry) Receptor antagonist Bridged Bicyclo Compounds Heterocyclic Bungarotoxins Macaca mulatta Kinetics medicine.anatomical_structure Nicotinic agonist nervous system Models Chemical Positron-Emission Tomography NMDA receptor Medicine Mental Health/Psychopharmacology Radiology and Medical Imaging/PET and SPECT Imaging Radiopharmaceuticals medicine.drug Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 3, Iss 9, p e3231 (2008) |
| ISSN: | 1932-6203 |
| Popis: | BackgroundThe alpha7 nicotinic acetylcholine receptors (nAChRs) play an important role in the pathophysiology of neuropsychiatric diseases such as schizophrenia and Alzheimer's disease. However, there are currently no suitable positron emission tomography (PET) radioligands for imaging alpha7 nAChRs in the intact human brain. Here we report the novel PET radioligand [11C]CHIBA-1001 for in vivo imaging of alpha7 nAChRs in the non-human primate brain.Methodology/principal findingsA receptor binding assay showed that CHIBA-1001 was a highly selective ligand at alpha7 nAChRs. Using conscious monkeys, we found that the distribution of radioactivity in the monkey brain after intravenous administration of [11C]CHIBA-1001 was consistent with the regional distribution of alpha7 nAChRs in the monkey brain. The distribution of radioactivity in the brain regions after intravenous administration of [11C]CHIBA-1001 was blocked by pretreatment with the selective alpha7 nAChR agonist SSR180711 (5.0 mg/kg). However, the distribution of [11C]CHIBA-1001 was not altered by pretreatment with the selective alpha4beta2 nAChR agonist A85380 (1.0 mg/kg). Interestingly, the binding of [11C]CHIBA-1001 in the frontal cortex of the monkey brain was significantly decreased by subchronic administration of the N-methyl-D-aspartate (NMDA) receptor antagonist phencyclidine (0.3 mg/kg, twice a day for 13 days); which is a non-human primate model of schizophrenia.Conclusions/significanceThe present findings suggest that [11C]CHIBA-1001 could be a novel useful PET ligand for in vivo study of the receptor occupancy and pathophysiology of alpha7 nAChRs in the intact brain of patients with neuropsychiatric diseases such as schizophrenia and Alzheimer's disease. |
| Databáze: | OpenAIRE |
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