title: Novel peripheral benzodiazepine receptor ligand [11C]DAA1106 for PET: an imaging tool for glial cells in the brain.
abstract: Peripheral benzodiazepine receptor (PBR) is expressed in most organs and its expression is reported to be increased in activated microglia in the brain. [(11)C]PK11195 has been widely used for the in vivo imaging of PBRs, but its signal in the brain was not high enough for stable quantitative analysis. We synthesized a novel positron emission tomography (PET) ligand, [(11)C]DAA1106, for PBR and investigated its in vivo properties in rat and monkey brain. High uptake of [(11)C]DAA1106 was observed in the olfactory bulb and choroid plexus area, followed by the pons/medulla and cerebellum by in vivo autoradiography of rat brain, correlating with the binding in vitro. [(11)C]DAA1106 binding was increased in the dorsal hippocampus with neural destruction, suggesting glial reaction. [(11)C]DAA1106 binding was both inhibited and displaced by 1.0 mg/kg of DAA1106 and 5 mg/kg of PK11195 by 80% and 70%, respectively. Specific binding was estimated as 80% of total binding. [(11)C]DAA1106 binding was four times higher compared to the binding of [(11)C]PK11195 in the monkey occipital cortex. These results indicated that [(11)C]DAA1106 might be a good ligand for in vivo imaging of PBR.
authors.affiliation: Brain Imaging Project, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Maeda
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Suhara
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
authors.forename: Takashi
authors.initials: T
authors.lastname: Okauchi
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Yasuno
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ikoma
authors.forename: Motoki
authors.initials: M
authors.lastname: Inaji
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nagai
authors.forename: Akihiro
authors.initials: A
authors.lastname: Takano
authors.forename: Shigeru
authors.initials: S
authors.lastname: Obayashi
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000081:Acetamides / Q000737:chemistry; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging; D008024:Ligands; D008253:Macaca mulatta; D008297:Male; D009457:Neuroglia / Q000000981:diagnostic imaging*; D010647:Phenyl Ethers / Q000737:chemistry; D011859:Radiography; D051381:Rats; D011963:Receptors, GABA-A / Q000096:biosynthesis*; D014055:Tomography, Emission-Computed
chemical_list: D000081:Acetamides; C118942:DAA 1106; D008024:Ligands; D010647:Phenyl Ethers; D011963:Receptors, GABA-A