title: Decreased in vivo availability of the cannabinoid type 2 receptor in Alzheimer's disease.
abstract: OBJECTIVE
  The cannabinoid type 2 receptor (CB2R) is expressed by immune cells such as monocytes and macrophages. In the brain, CB2R is primarily found on microglia. CB2R upregulation has been reported in animal models of Alzheimer's disease, with a preferential localization near amyloid beta (Aβ) plaques, and in patients post mortem. We performed in vivo brain imaging and kinetic modelling of the CB2R tracer [11C]NE40 in healthy controls (HC) and in patients with Alzheimer's disease (AD) to investigate whether higher CB2R availability regionally colocalized to Aβ deposits is present in vivo.
  
  
  METHODS
  Dynamic 90-min [11C]NE40 PET scans were performed in eight HC and nine AD patients with full kinetic modelling using arterial sampling and metabolite correction and partial volume correction. All AD patients received a static [11C]PIB scan 40 min after injection. In four HC, a retest scan with [11C]NE40 PET was performed within 9 weeks to investigate test-retest characteristics.
  
  
  RESULTS
  [11C]NE40 was metabolized quickly leading to 50 % of intact tracer 20 min after injection and 20 % at 90 min. A two-tissue kinetic model fitted most of the time-activity curves best; both binding potential (BPND) and distribution volume (VT) parameters could be used. Brain uptake was generally low with an average K1value of 0.07 ml/min/ml tissue. VTand BPNDwere in the range of 0.7 - 1.8 and 0.6 - 1.6, respectively. Test values in HC were about 30 % for VTand BPND. AD patients showed overall significantly lower CB2R binding. No relationship was found between regional or global amyloid load and CB2R availability.
  
  
  CONCLUSIONS
  Kinetic modelling of [11C]NE40 is possible with a two-tissue reversible model. In contrast to preclinical and post-mortem data, [11C]NE40 PET shows lower CB2R availability in vivo in AD patients, with no relationship to Aβ plaques. A possible explanation for these findings is that [11C]NE40 binds to CB2R with lower affinity and/or selectivity than to CB1R.
authors.affiliation: Department of Imaging & Pathology, Nuclear Medicine and Molecular Imaging, KU Leuven and University Hospitals Leuven, Leuven, Belgium. Rawaha.ahmad@uzleuven.be.|Division of Nuclear Medicine, University Hospital Leuven, Herestraat 49 E901, 3000, Leuven, Belgium. Rawaha.ahmad@uzleuven.be.
authors.forename: Rawaha
authors.initials: R
authors.lastname: Ahmad
authors.affiliation: Department of Imaging & Pathology, Nuclear Medicine and Molecular Imaging, KU Leuven and University Hospitals Leuven, Leuven, Belgium.|National Research Nuclear University MEPhI, Moscow, Russia.
authors.forename: Andrey
authors.initials: A
authors.lastname: Postnov
authors.affiliation: Laboratory for Radiopharmacy, KU Leuven, Leuven, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Bormans
authors.affiliation: Department of Neurology, University Hospital Brussels, Brussels, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Versijpt
authors.affiliation: Old Age Psychiatry, Department of Psychiatry, KU Leuven and University Hospitals Leuven, Leuven, Belgium.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Vandenbulcke
authors.affiliation: Department of Imaging & Pathology, Nuclear Medicine and Molecular Imaging, KU Leuven and University Hospitals Leuven, Leuven, Belgium.|Division of Nuclear Medicine, University Hospital Leuven, Herestraat 49 E901, 3000, Leuven, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Van Laere
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D001682:Biological Availability; D001921:Brain / Q000378:metabolism*; D003198:Computer Simulation; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008959:Models, Neurological; D057054:Molecular Imaging / Q000379:methods; D058225:Plaque, Amyloid / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods; D011804:Quinolines / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: C576981:2-oxo-7-methoxy-8-butyloxy-1,2-dihydroquinoline-3-carboxylic acid cyclohexylamide; C588309:CNR2 protein, human; D011804:Quinolines; D019275:Radiopharmaceuticals; D043885:Receptor, Cannabinoid, CB2
keywords: Alzheimer’s disease; CB2R; Cannabinoid type 2 receptor; Neuroinflammation; PET imaging