title: Evaluation of cannabinoid type 1 receptor expression in the rat brain using [¹⁸F]MK-9470 microPET.
abstract: OBJECTIVE
  The ligand [(18)F]MK-9470 is an inverse agonist binding with high affinity and specificity to the cannabinoid type 1 (CB1) receptor. In this study, a semiquantitative acquisition and analysis protocol for investigation of the CB1 receptor distribution in the rat brain was established.
  
  
  METHODS
  Two C57BL/6N mice (one CB1 (-/-) and one wild-type) and 19 Sprague Dawley rats were investigated using a Focus 120 microPET scanner. Seven rats were scanned twice for test-retest evaluation, six rats were scanned for blocking experiments using the inverse CB1 receptor agonist rimonabant, and 19 rats were scanned for baseline studies. Percentage injected dose per millilitre (%ID/ml) or uptake ratios (VOItarget/VOIwhole brain) were calculated. A Bland-Altman-plot was computed and mean values were compared using a two-sided paired t test.
  
  
  RESULTS
  Comparing the data from the CB1 (-/-) mouse and the wild-type mouse, [(18)F]MK-9470 showed good specificity. Regarding the rat data, there was no relationship between the difference between the test and retest measurements or their mean value. The test and retest data showed a strong correlation (ρ c = 0.846, p ≤ 0.01; r Pearson = 0.857). Equivalence was not found for all regions and not even in the pons at baseline or under blocking condition. Only the baseline studies showed the highest levels of uptake in the caudate-putamen and thalamus, whereas moderate uptake was found in the hippocampus, hypothalamus and cerebellum, and the lowest uptake was observed in the cortex, amygdala and pons.
  
  
  CONCLUSIONS
  A reference region is not available; however, the proposed analysis method using the parameter uptake ratio is simple and delivers stable results allowing the discrimination of distinct brain regions.
authors.affiliation: Department of Nuclear Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstraße 1, 55131, Mainz, Germany, isabelle.miederer@unimedizin-mainz.de.
authors.forename: I
authors.initials: I
authors.lastname: Miederer
authors.forename: S
authors.initials: S
authors.lastname: Maus
authors.forename: I
authors.initials: I
authors.lastname: Zwiener
authors.forename: G
authors.initials: G
authors.lastname: Podoprygorina
authors.forename: D
authors.initials: D
authors.lastname: Meshcheryakov
authors.forename: B
authors.initials: B
authors.lastname: Lutz
authors.forename: M
authors.initials: M
authors.lastname: Schreckenberger
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C528731:MK-9470; D011725:Pyridines; D043884:Receptor, Cannabinoid, CB1