title: Comparison of two PET radioligands, [11C]FPEB and [11C]SP203, for quantification of metabotropic glutamate receptor 5 in human brain.
abstract: Of the two18F-labeled PET ligands currently available to image metabotropic glutamate receptor 5 (mGluR5), [18F]FPEB is reportedly superior because [18F]SP203 undergoes glutathionlyation, generating [18F]-fluoride ion that accumulates in brain and skull. To allow multiple PET studies on the same day with lower radiation exposure, we prepared [11C]FPEB and [11C]SP203 from [11C]hydrogen cyanide and compared their abilities to accurately quantify mGluR5 in human brain, especially as regards radiometabolite accumulation. Genomic plot was used to estimate the ratio of specific-to-nondisplaceable uptake ( BPND) without using a receptor blocking drug. Both tracers quantified mGluR5; however [11C]SP203, like [18F]SP203, had radiometabolite accumulation in brain, as evidenced by increased distribution volume ( VT) over the scan period. Absolute VTvalues were ∼30% lower for11C-labeled compared with18F-labeled radioligands, likely caused by the lower specific activities (and high receptor occupancies) of the11C radioligands. The genomic plot indicated ∼60% specific binding in cerebellum, which makes it inappropriate as a reference region. Whole-body scans performed in healthy subjects demonstrated a low radiation burden typical for11C-ligands. Thus, the evidence suggests that [11C]FPEB is superior to [11C]SP203. If prepared in higher specific activity, [11C]FPEB would presumably be as effective as [18F]FPEB for quantifying mGluR5 in human brain.
authors.affiliation: 1 Molecular Imaging Branch, National Institute of Mental Health, Bethesda, USA.
authors.forename: Talakad G
authors.initials: TG
authors.lastname: Lohith
authors.affiliation: 1 Molecular Imaging Branch, National Institute of Mental Health, Bethesda, USA.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tsujikawa
authors.affiliation: 1 Molecular Imaging Branch, National Institute of Mental Health, Bethesda, USA.
authors.forename: Fabrice G
authors.initials: FG
authors.lastname: Siméon
authors.affiliation: 1 Molecular Imaging Branch, National Institute of Mental Health, Bethesda, USA.|2 Department of Neuroimaging, King's College London, London, UK.
authors.forename: Mattia
authors.initials: M
authors.lastname: Veronese
authors.affiliation: 1 Molecular Imaging Branch, National Institute of Mental Health, Bethesda, USA.
authors.forename: Sami S
authors.initials: SS
authors.lastname: Zoghbi
authors.affiliation: 1 Molecular Imaging Branch, National Institute of Mental Health, Bethesda, USA.
authors.forename: Chul Hyoung
authors.initials: CH
authors.lastname: Lyoo
authors.affiliation: 1 Molecular Imaging Branch, National Institute of Mental Health, Bethesda, USA.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: 1 Molecular Imaging Branch, National Institute of Mental Health, Bethesda, USA.
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Morse
authors.affiliation: 1 Molecular Imaging Branch, National Institute of Mental Health, Bethesda, USA.
authors.forename: Victor W
authors.initials: VW
authors.lastname: Pike
authors.affiliation: 1 Molecular Imaging Branch, National Institute of Mental Health, Bethesda, USA.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujita
authors.affiliation: 1 Molecular Imaging Branch, National Institute of Mental Health, Bethesda, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Innis
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002250:Carbon Radioisotopes; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008024:Ligands; D008297:Male; D008954:Models, Biological; D009570:Nitriles / Q000097:blood / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods*; D011725:Pyridines / Q000097:blood / Q000493:pharmacokinetics*; D012333:RNA, Messenger / Q000235:genetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D064529:Receptor, Metabotropic Glutamate 5 / Q000235:genetics / Q000378:metabolism*; D013844:Thiazoles / Q000097:blood / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D051598:Whole Body Imaging
chemical_list: C527000:3-fluoro-5-((pyridin-3-yl)ethynyl)benzonitrile; C522844:3-fluoro-5-(2-(2-(fluoromethyl)thiazol-4-yl)ethynyl)benzonitrile; D002250:Carbon Radioisotopes; C578935:GRM5 protein, human; D008024:Ligands; D009570:Nitriles; D011725:Pyridines; D012333:RNA, Messenger; D019275:Radiopharmaceuticals; D064529:Receptor, Metabotropic Glutamate 5; D013844:Thiazoles
keywords: FPEB; PET imaging; SP203; genomic plot; mGluR5