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Journal of Nuclear Medicine

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OtherBASIC SCIENCE INVESTIGATIONS

Radiosynthesis and Preclinical Evaluation of 11C-ABP688 as a Probe for Imaging the Metabotropic Glutamate Receptor Subtype 5

Simon M. Ametamey, Lea J. Kessler, Michael Honer, Matthias T. Wyss, Alfred Buck, Samuel Hintermann, Yves P. Auberson, Fabrizio Gasparini and Pius A. Schubiger
Journal of Nuclear Medicine April 2006, 47 (4) 698-705;
Simon M. Ametamey
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Lea J. Kessler
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Michael Honer
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Matthias T. Wyss
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Alfred Buck
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Samuel Hintermann
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Yves P. Auberson
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Fabrizio Gasparini
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Pius A. Schubiger
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Figures

  • FIGURE 1. 
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    FIGURE 1. 

    Structures of 11C-M-MPEP, 11C-M-FPEP, 18F-FE-MPEP, 18F-FPEP, and 11C-ABP688.

  • FIGURE 2. 
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    FIGURE 2. 

    Radiosynthesis of 11C-ABP688.

  • FIGURE 3. 
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    FIGURE 3. 

    (A) Typical saturation curve of 11C-ABP688 binding to rat brain membrane. (B) Representative Scatchard plot of 11C-ABP688 binding. Results from 3 independent determinations gave a KD of 1.7 ± 0.2 nmol/L and a Bmax of 231 ± 18 fmol/mg of protein.

  • FIGURE 4. 
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    FIGURE 4. 

    (A) Autoradiographic illustration of 20-μm unwashed horizontal (approximately −4.10 mm from Bregma and 5.90 mm interaural (24) slice of rat brain 8 min after intravenous injection of 11C-ABP688. (B and C) Series of horizontal slices of 11C-ABP688 distribution in wt-mouse (B) and ko-mouse (C).

  • FIGURE 5. 
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    FIGURE 5. 

    11C-ABP688 uptake in some brain regions of rat and in blood. Animals were sacrificed 30 min after injection. Control group (n = 3) received polyethylene glycol:H2O (1:1) and 11C-ABP688, and test group (n = 3) received coinjection of M-MPEP (1.0 mg/kg of body weight) and 11C-ABP688. Data are expressed as percentage normalized injected dose (%ID norm) per gram of tissue ± SD.

  • FIGURE 6. 
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    FIGURE 6. 

    Biodistribution of 11C-ABP688 in some brain regions of wt-mice (n = 4), mGluR5-ko-mice (n = 4), and blood. Animals were sacrificed 20 min after injection, and data are expressed as percentage of normalized injected dose (%ID norm) per gram of tissue ± SD.

  • FIGURE 7. 
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    FIGURE 7. 

    Representative horizontal images of 11C-ABP688 uptake in head of 2 rats. Control animal (A and B) received 29.4 MBq (injected mass, 1.3 nmol) of radiotracer, and test animal (C and D) received coinjection of M-MPEP (1.0 mg/kg of body weight) and 11C-ABP688 (5.37 MBq, injected mass, 1.7 nmol). Images were normalized to injected radioactivity and body weight. Data were reconstructed with bin size of 0.3 mm from 0 to 30 min after injection. ce = cerebellum; cp = caudate putamen; hi = hippocampus; lg = lacrimal gland. In B and D, whole brain and specific regions are bordered with white (24).

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Journal of Nuclear Medicine: 47 (4)
Journal of Nuclear Medicine
Vol. 47, Issue 4
April 2006
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Radiosynthesis and Preclinical Evaluation of 11C-ABP688 as a Probe for Imaging the Metabotropic Glutamate Receptor Subtype 5
Simon M. Ametamey, Lea J. Kessler, Michael Honer, Matthias T. Wyss, Alfred Buck, Samuel Hintermann, Yves P. Auberson, Fabrizio Gasparini, Pius A. Schubiger
Journal of Nuclear Medicine Apr 2006, 47 (4) 698-705;

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Radiosynthesis and Preclinical Evaluation of 11C-ABP688 as a Probe for Imaging the Metabotropic Glutamate Receptor Subtype 5
Simon M. Ametamey, Lea J. Kessler, Michael Honer, Matthias T. Wyss, Alfred Buck, Samuel Hintermann, Yves P. Auberson, Fabrizio Gasparini, Pius A. Schubiger
Journal of Nuclear Medicine Apr 2006, 47 (4) 698-705;
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  • Marked global reduction in mGluR5 receptor binding in smokers and ex-smokers determined by [11C]ABP688 positron emission tomography
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