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, [18F]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 [18F]MK-9470 PET. Parametric [18F]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 [18F]MK-9470 binding to CB1R increased with aging but only in women (pFWE<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 [18F]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 [18F]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.
Year
DOI
Venue
2008
10.1016/j.neuroimage.2007.10.053
NeuroImage
Keywords
Field
DocType
Cannabinoid-type 1 receptor,PET,Aging,Gender,Statistical parametric mapping
MK-9470,Developmental psychology,Radioligand,Ligand (biochemistry),Internal medicine,Psychology,Receptor,In vivo,Statistical parametric mapping,Cannabinoid,Endocannabinoid system,Endocrinology
Journal
Volume
Issue
ISSN
39
4
1053-8119
Citations 
PageRank 
References 
5
0.98
1
Authors
7
Name
Order
Citations
PageRank
Koen Van Laere151.66
Karolien Goffin281.43
Cindy Casteels361.86
P Dupont420624.57
Mortelmans, L.561.42
Jan de Hoon681.47
Guy Bormans7244.76