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Gender-dependent increases with healthy aging of the human cerebral cannabinoid-type 1 receptor binding using [18F]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.
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“That report found greater plasma parent fraction and higher normalized brain uptake (SUV) in men, which is consistent with our findings.”
From Elevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: A positron emission tomography study (2013) · cites this paper as [59]
In the citing paper
“Our results are largely in agreement with a previous study that used the CB1 PET tracer [18F]MK-9470 to investigate the effects of age and gender59.”
From Elevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: A positron emission tomography study (2013) · cites this paper as [59]
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Metadata
- Authors
- Van Laere, K., Goffin, K., Casteels, C., Dupont, P., Mortelmans, L., de Hoon, J., & Bormans, G.
- Affiliations
- Universitair Ziekenhuis Leuven (BE)
- KU Leuven (BE)
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2008-02
- Volume
- 39
- Issue
- 4
- Pages
- 1533-1541
- ISSN
- 1053-8119 (ISSN-L)
- OpenAlex
- W2088851718
- Cited by
- 142
- References
- 53
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 9 · 2023: 8 · 2022: 14 · 2021: 8 · 2020: 10 · 2019: 8 · 2018: 7 · 2017: 3 · 2016: 4 · 2015: 4 · 2014: 11 · 2013: 11 · 2012: 6
- FWCI
- 3.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- Lirias (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- cannabinoid type 1 receptor, CB1R, endocannabinoid system, healthy aging, sex differences, positron emission tomography, hippocampus, basal ganglia, limbic system, sex hormones, receptor binding
- MeSH terms
- Adolescent, Adult, Aged, Aging, Brain, Brain Chemistry, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Pyridines, Reference Values, Sex Characteristics, Radiopharmaceuticals, Area Under Curve, Receptor, Cannabinoid, CB1, Positron-Emission Tomography
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