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@ARTICLE{Elmenhorst:10453,
      author       = {Elmenhorst, D. and Minuzzi, L. and Aliaga, A. and Rowley,
                      J. and Massarweh, G. and Diksic, M. and Bauer, A. and
                      Rosa-Neto, P.},
      title        = {{I}n vivo and in vitro validation of reference tissue
                      models for the m{G}lu{R}5 ligand (11{C}){ABP}688},
      journal      = {Journal of cerebral blood flow $\&$ metabolism},
      volume       = {30},
      issn         = {0271-678X},
      address      = {[s.l.]},
      publisher    = {Ovid},
      reportid     = {PreJuSER-10453},
      pages        = {1538 - 1549},
      year         = {2010},
      note         = {This study was supported by the Alzheimer's Association new
                      investigator grant, the Heinrich Hertz Foundation of the
                      Ministry of Science and Technology, North-Rhine Westfalia,
                      Germany (DE), Fonds de la Recherche en Sante du Quebec
                      (FRSQ), Chercheur Burcier Award, Nussia and Andre Aisenstadt
                      Foundation and Fondation Savoy.},
      abstract     = {The primary objective of this study was to verify the
                      suitability of reference tissue-based quantification methods
                      of the metabotropic glutamate receptor type 5 (mGluR(5))
                      with [(11)C]ABP688. This study presents in vivo (Positron
                      Emission Tomography (PET)) and in vitro (autoradiography)
                      measurements of mGluR(5) densities in the same rats and
                      evaluates both noninvasive and blood-dependent
                      pharmacokinetic models for the quantification of
                      [(11)C]ABP688 binding. Eleven rats underwent [(11)C]ABP688
                      PET scans. In five animals, baseline scans were compared
                      with blockade experiments with the antagonist
                      1,2-methyl-6-(phenylethynyl)-pyridine (MPEP), and arterial
                      blood samples were drawn and corrected for metabolites.
                      Afterward, saturation-binding autoradiography was performed.
                      Blocking with MPEP resulted in an average decrease of the
                      total distribution volume (V(T)) between $43\%$ and $58\%$
                      (thalamus and caudate-putamen, respectively) but had no
                      significant effect on cerebellar V(T) (mean reduction:
                      $-0.01\%).$ Comparing binding potential (BP(ND)) based on
                      the V(T) with noninvasively determined BP(ND) revealed an
                      average negative bias of $0.7\%$ in the caudate-putamen and
                      an average positive bias of $3.1\%$ in the low-binding
                      regions. Scan duration of 50 minutes is required. The
                      cerebellum is a suitable reference region for the
                      quantification of mGluR(5) availability as measured with
                      [(11)C]ABP688 PET in rats. Blood-based and reference
                      region-based PET quantification shows a significant linear
                      relationship to autoradiographic determinations.},
      keywords     = {Animals / Autoradiography: methods / Binding Sites / Brain:
                      metabolism / Brain: radionuclide imaging / Carbon
                      Radioisotopes: analysis / Carbon Radioisotopes: metabolism /
                      Carbon Radioisotopes: pharmacokinetics / Kinetics / Male /
                      Oximes: analysis / Oximes: metabolism / Oximes:
                      pharmacokinetics / Positron-Emission Tomography: methods /
                      Pyridines: analysis / Pyridines: metabolism / Pyridines:
                      pharmacokinetics / Rats / Rats, Sprague-Dawley / Receptors,
                      Metabotropic Glutamate: analysis / Receptors, Metabotropic
                      Glutamate: metabolism /
                      3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime
                      (NLM Chemicals) / Carbon Radioisotopes (NLM Chemicals) /
                      Oximes (NLM Chemicals) / Pyridines (NLM Chemicals) /
                      Receptors, Metabotropic Glutamate (NLM Chemicals) /
                      metabotropic glutamate receptor 5 (NLM Chemicals) / J
                      (WoSType)},
      cin          = {INM-2},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-2-20090406},
      pnm          = {Funktion und Dysfunktion des Nervensystems (FUEK409) /
                      89574 - Theory, modelling and simulation (POF2-89574)},
      pid          = {G:(DE-Juel1)FUEK409 / G:(DE-HGF)POF2-89574},
      shelfmark    = {Endocrinology $\&$ Metabolism / Hematology / Neurosciences},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:20531460},
      pmc          = {pmc:PMC2949244},
      UT           = {WOS:000280561900013},
      doi          = {10.1038/jcbfm.2010.65},
      url          = {https://juser.fz-juelich.de/record/10453},
}