title: Type 1 cannabinoid receptor mapping with [18F]MK-9470 PET in the rat brain after quinolinic acid lesion: a comparison to dopamine receptors and glucose metabolism.
abstract: OBJECTIVE
  Several lines of evidence imply early alterations in metabolic, dopaminergic and endocannabinoid neurotransmission in Huntington's disease (HD). Using [18F]MK-9470 and small animal PET, we investigated cerebral changes in type 1 cannabinoid (CB1) receptor binding in the quinolinic acid (QA) rat model of HD in relation to glucose metabolism, dopamine D2 receptor availability and amphetamine-induced turning behaviour.
  
  
  METHODS
  Twenty-one Wistar rats (11 QA and 10 shams) were investigated. Small animal PET acquisitions were conducted on a Focus 220 with approximately 18 MBq of [18F]MK-9470, [18F]FDG and [11C]raclopride. Relative glucose metabolism and parametric CB1 receptor and D2 binding images were anatomically standardized to Paxinos space and analysed voxel-wise using Statistical Parametric Mapping (SPM2).
  
  
  RESULTS
  In the QA model, [18F]MK-9470 uptake, glucose metabolism and D2 receptor binding were reduced in the ipsilateral caudate-putamen by 7, 35 and 77%, respectively (all p<2.10(-5)), while an increase for these markers was observed on the contralateral side (>5%, all p<7.10(-4)). [18F]MK-9470 binding was also increased in the cerebellum (p=2.10(-5)), where it was inversely correlated to the number of ipsiversive turnings (p=7.10(-6)), suggesting that CB1 receptor upregulation in the cerebellum is related to a better functional outcome. Additionally, glucose metabolism was relatively increased in the contralateral hippocampus, thalamus and sensorimotor cortex (p=1.10(-6)).
  
  
  CONCLUSIONS
  These data point to in vivo changes in endocannabinoid transmission, specifically for CB1 receptors in the QA model, with involvement of the caudate-putamen, but also distant regions of the motor circuitry, including the cerebellum. These data also indicate the occurrence of functional plasticity on metabolism, D2 and CB1 neurotransmission in the contralateral hemisphere.
authors.affiliation: Division of Nuclear Medicine, KU Leuven and University Hospital Leuven, Leuven, Belgium. cindy.casteels@med.kuleuven.be
authors.forename: Cindy
authors.initials: C
authors.lastname: Casteels
authors.forename: Emili
authors.initials: E
authors.lastname: Martinez
authors.forename: Guy
authors.initials: G
authors.lastname: Bormans
authors.forename: Lluïsa
authors.initials: L
authors.lastname: Camon
authors.forename: Núria
authors.initials: N
authors.lastname: de Vera
authors.forename: Veerle
authors.initials: V
authors.lastname: Baekelandt
authors.forename: Anna M
authors.initials: AM
authors.lastname: Planas
authors.forename: Koen
authors.initials: K
authors.lastname: Van Laere
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006816:Huntington Disease / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D011725:Pyridines / Q000493:pharmacokinetics*; D017378:Quinolinic Acid; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: C528731:MK-9470; D011725:Pyridines; D019275:Radiopharmaceuticals; D043884:Receptor, Cannabinoid, CB1; D011954:Receptors, Dopamine; D017378:Quinolinic Acid; D005947:Glucose