title: Gender-dependent increases with healthy aging of the human cerebral cannabinoid-type 1 receptor binding using [(18)F]MK-9470 PET.
abstract: The endocannabinoid system (ECS) is implicated as a regulator of homeostasis of several cerebral functions and is a novel target for drug treatment of neuropyschiatric disorders. So far, the cerebral cannabinoid-type 1 receptor (CB1R) has only been studied using in vitro, animal model, electrophysiological and post-mortem data. We have used positron emission tomography (PET) using a high-affinity, subtype-selective radioligand, [(18)F]MK-9470, to assess the in vivo cerebral CB1R distribution and its variation with healthy aging and gender. Fifty healthy volunteers (25 M/25 F, 18-69 years) underwent [(18)F]MK-9470 PET. Parametric [(18)F]MK-9470 binding maps were constructed, corrected for partial volume effects and analyzed using statistical parametric mapping in a combined categorical (gender) and covariate (age) design. We found that [(18)F]MK-9470 binding to CB1R increased with aging but only in women (p(FWE)<0.05, corrected for multiple comparisons); this was most pronounced in the basal ganglia, lateral temporal cortex and limbic system, especially in the hippocampus. Men showed higher [(18)F]MK-9470 binding then women (p<0.001, uncorrected), in clusters of the limbic system and cortico-striato-thalamic-cortical circuit. Region-dependent and gender-related upregulation of [(18)F]MK-9470 binding with aging is in line with ex vivo findings in rodent studies and may be associated with a changing homeostatic capacity or compensation mechanisms in the ECS that is modulated by sex hormones. In vivo PET of the CB1R will likely improve our understanding of the ECS in several neurological and psychiatric disorders.
authors: Division of Nuclear Medicine, University Hospital and KU Leuven, Belgium. koen.vanlaere@uzleuven.be
authors: Koen
authors: K
authors: Van Laere
authors: Karolien
authors: K
authors: Goffin
authors: Cindy
authors: C
authors: Casteels
authors: Patrick
authors: P
authors: Dupont
authors: Luc
authors: L
authors: Mortelmans
authors: Jan
authors: J
authors: de Hoon
authors: Guy
authors: G
authors: Bormans
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D019540:Area Under Curve; D001921:Brain / Q000000981:diagnostic imaging*; D001923:Brain Chemistry / Q000502:physiology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D012016:Reference Values; D012727:Sex Characteristics
chemical_list: C528731:MK-9470; D011725:Pyridines; D019275:Radiopharmaceuticals; D043884:Receptor, Cannabinoid, CB1