In vivo and in vitro validation of reference tissue models for the mGluR(5) ligand [(11)C]ABP688

J Cereb Blood Flow Metab. 2010 Aug;30(8):1538-49. doi: 10.1038/jcbfm.2010.65. Epub 2010 Jun 9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoradiography / methods
  • Binding Sites
  • Brain / diagnostic imaging*
  • Brain / metabolism
  • 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
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / analysis
  • Receptors, Metabotropic Glutamate / metabolism*


  • 3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime
  • Carbon Radioisotopes
  • Oximes
  • Pyridines
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate