Cannabinoid Receptor Type 1 in Parkinson's Disease : A Positron Emission Tomography Study with [F-18]FMPEP-d(2)

Background The endocannabinoid system is a widespread neuromodulatory system affecting several biological functions and processes. High densities of type 1 cannabinoid (CB1) receptors and endocannabinoids are found in basal ganglia, which makes them an interesting target group for drug development in basal ganglia disorders such as Parkinson's disease (PD). Objective The aim of this study was to investigate CB1 receptors in PD with [F-18]FMPEP-d(2) positron emission tomography (PET) and the effect of dopaminergic medication on the [F-18]FMPEP-d(2) binding. Methods The data consisted of 16 subjects with PD and 10 healthy control subjects (HCs). All participants underwent a [F-18]FMPEP-d(2) high-resolution research tomograph PET examination for the quantitative assessment of cerebral binding to CB1 receptors. To investigate the effect of dopaminergic medication on the [F-18]FMPEP-d(2) binding, 15 subjects with PD underwent [F-18]FMPEP-d(2) PET twice, both on and off antiparkinsonian medication. Results [F-18]FMPEP-d(2) distribution volume was significantly lower in the off scan compared with the on scan in basal ganglia, thalamus, hippocampus, and amygdala (P < 0.05). Distribution volume was lower in subjects with PD off than in HCs globally (P < 0.05), but not higher than in HCs in any brain region. Conclusions Subjects with PD have lower CB1 receptor availability compared with HCs. PD medication increases CB1 receptor toward normal levels. (c) 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder SocietyPeer reviewe

Cannabinoid Receptor Type 1 in Parkinson's Disease: A Positron Emission Tomography Study with [F-18]FMPEP-d(2)

Background: The endocannabinoid system is a widespread neuromodulatory system affecting several biological functions and processes. High densities of type 1 cannabinoid (CB1) receptors and endocannabinoids are found in basal ganglia, which makes them an interesting target group for drug development in basal ganglia disorders such as Parkinson's disease (PD). Objective: The aim of this study was to investigate CB1 receptors in PD with [18F]FMPEP-d2 positron emission tomography (PET) and the effect of dopaminergic medication on the [18F]FMPEP-d2 binding. Methods: The data consisted of 16 subjects with PD and 10 healthy control subjects (HCs). All participants underwent a [18F]FMPEP-d2 high-resolution research tomograph PET examination for the quantitative assessment of cerebral binding to CB1 receptors. To investigate the effect of dopaminergic medication on the [18F]FMPEP-d2) binding, 15 subjects with PD underwent [18F]FMPEP-d2 PET twice, both on and off antiparkinsonian medication. Results: [18F]FMPEP-d2 distribution volume was significantly lower in the off scan compared with the on scan in basal ganglia, thalamus, hippocampus, and amygdala (P off than in HCs globally (P Conclusions: Subjects with PD have lower CB1 receptor availability compared with HCs. PD medication increases CB1 receptor toward normal levels. (c) 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society</p

Effects of age, BMI and sex on the glial cell marker TSPO : a multicentre [11C]PBR28 HRRT PET study

Purpose The purpose of this study was to investigate the effects of ageing, sex and body mass index (BMI) on translocator protein (TSPO) availability in healthy subjects using positron emission tomography (PET) and the radioligand [C-11]PBR28. Methods [C-11]PBR28 data from 140 healthy volunteers (72 males and 68 females; N = 78 with HAB and N = 62 MAB genotype; age range 19-80 years; BMI range 17.6-36.9) were acquired with High Resolution Research Tomograph at three centres: Karolinska Institutet (N = 53), Turku PET centre (N = 62) and Yale University PET Center (N = 25). The total volume of distribution (V-T) was estimated in global grey matter, frontal, temporal, occipital and parietal cortices, hippocampus and thalamus using multilinear analysis 1. The effects of age, BMI and sex on TSPO availability were investigated using linear mixed effects model, with TSPO genotype and PET centre specified as random intercepts. Results There were significant positive correlations between age and V-T in the frontal and temporal cortex. BMI showed a significant negative correlation with V-T in all regions. Additionally, significant differences between males and females were observed in all regions, with females showing higher V-T. A subgroup analysis revealed a positive correlation between V-T and age in all regions in male subjects, whereas age showed no effect on TSPO levels in female subjects. Conclusion These findings provide evidence that individual biological properties may contribute significantly to the high variation shown in TSPO binding estimates, and suggest that age, BMI and sex can be confounding factors in clinical studies