title: [carbonyl-11C]4-Fluoro-N-methyl-N-(4-(6-(methylamino)pyrimidin-4-yl)thiazol-2-yl)benzamide ([11C]FIMX) is an effective radioligand for PET imaging of metabotropic glutamate receptor 1 (mGluR1) in monkey brain.
abstract: BACKGROUND
  Metabotropic glutamate subtype receptor 1 (mGluR1) is implicated in several neuropsychiatric disorders and is a target for drug development. [(18)F]FIMX ([(18)F]4-fluoro--N-methyl-N--(4-(6-(methylamino)pyrimidin-4-yl)thiazol-2-yl)benzamide) is an effective radioligand for imaging brain mGluR1 with PET. A similarly effective radioligand with a shorter half-life would usefully allow PET studies of mGluR1 at baseline and after pharmacological or other challenge on the same day. Here we describe the preparation of [(11)C]FIMX for evaluation in monkey with PET.
  
  
  METHODS
  [(11)C]FIMX was prepared via Pd-promoted carbonylation of 1-fluoro-4-iodobenzene with [(11)C]carbon monoxide, aminolysis of the [(11)C]acyl-palladium complex with the requisite Boc-protected amine, and deprotection with HCl in THF. PET scans of [(11)C]FIMX injected into a monkey were performed at baseline and after preblock of mGluR1 with measurement of the arterial input function.
  
  
  RESULTS
  The radiosynthesis required 42 min and gave [(11)C]FIMX in about 5% overall decay-corrected radiochemical yield and with a specific activity of about 100 GBq/μmol. PET in rhesus monkey at baseline showed that radioactivity peaked high in receptor-rich cerebellum and much lower in receptor-poor occipital cortex. Radioactivity in cerebellum declined to 32% of peak at 85 min. VT at baseline appeared stable in all brain regions after 60 min. Under mGluR1 pre-blocked condition, radioactivity uptake in all regions declined more rapidly to a low level. Receptor pre-block reduced VT from 13.0 to 1.5 in cerebellum and from 2.9 to 1.4 in occipital cortex.
  
  
  CONCLUSIONS
  [(11)C]FIMX is an effective radioligand for imaging mGluR1 in monkey with PET.
authors: Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Building 10, Room B3 C346A, 10 Center Drive, Bethesda, MD, 20892-1003, United States.
authors: Jinsoo
authors: J
authors: Hong
authors: Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Building 10, Room B3 C346A, 10 Center Drive, Bethesda, MD, 20892-1003, United States.
authors: Shuiyu
authors: S
authors: Lu
authors: Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Building 10, Room B3 C346A, 10 Center Drive, Bethesda, MD, 20892-1003, United States.
authors: Rong
authors: R
authors: Xu
authors: Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Building 10, Room B3 C346A, 10 Center Drive, Bethesda, MD, 20892-1003, United States.
authors: Jeih-San
authors: JS
authors: Liow
authors: Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Building 10, Room B3 C346A, 10 Center Drive, Bethesda, MD, 20892-1003, United States.
authors: Alicia E
authors: AE
authors: Woock
authors: Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Building 10, Room B3 C346A, 10 Center Drive, Bethesda, MD, 20892-1003, United States.
authors: Kimberly J
authors: KJ
authors: Jenko
authors: Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Building 10, Room B3 C346A, 10 Center Drive, Bethesda, MD, 20892-1003, United States.
authors: Robert L
authors: RL
authors: Gladding
authors: Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Building 10, Room B3 C346A, 10 Center Drive, Bethesda, MD, 20892-1003, United States.
authors: Sami S
authors: SS
authors: Zoghbi
authors: Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Building 10, Room B3 C346A, 10 Center Drive, Bethesda, MD, 20892-1003, United States.
authors: Robert B
authors: RB
authors: Innis
authors: Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Building 10, Room B3 C346A, 10 Center Drive, Bethesda, MD, 20892-1003, United States. Electronic address: pikev@mail.nih.gov.
authors: Victor W
authors: VW
authors: Pike
mesh_terms: D000818:Animals; D001549:Benzamides / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics*; D004353:Drug Evaluation, Preclinical; D007091:Image Processing, Computer-Assisted; D008253:Macaca mulatta; D049268:Positron-Emission Tomography / Q000379:methods*; D011854:Radiochemistry; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D013844:Thiazoles / Q000493:pharmacokinetics*
chemical_list: C586005:4-fluoro-N-methyl-N-(4-(6-(methylamino)pyrimidin-4-yl)thiazol-2-yl)benzamide; D001549:Benzamides; D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D018094:Receptors, Metabotropic Glutamate; D013844:Thiazoles; C104077:metabotropic glutamate receptor type 1
keywords: Brain; Carbon-11; Monkey; PET; Radioligand; mGluR1