量研学術機関リポジトリ「QST-Repository」は、国立研究開発法人 量子科学技術研究開発機構に所属する職員等が生み出した学術成果（学会誌発表論文、学会発表、研究開発報告書、特許等）を集積しインターネット上で広く公開するサービスです。 Welcome to QST-Repository where we accumulates and discloses the academic research results(Journal Publications, Conference presentation, Research and Development Report, Patent, etc.) of the members of National Institutes for Quantum Science and Technology.
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Purpose Monoacylglycerol lipase (MAGL) regulates cannabinoid neurotransmission and the pro-infammatory arachidonic
acid pathway by degrading endocannabinoids. MAGL inhibitors may accordingly act as cannabinoid-potentiating and antiinfammatory agents. Although MAGL dysfunction has been implicated in neuropsychiatric disorders, it has never been
visualized in vivo in human brain. The primary objective of the current study was to visualize MAGL in the human brain
using the novel PET ligand 18F-T-401.
Methods Seven healthy males underwent 120-min dynamic 18F-T-401-PET scans with arterial blood sampling. Six subjects also underwent a second PET scan with 18F-T-401 within 2 weeks of the frst scan. For quantifcation of MAGL in the
human brain, kinetic analyses using one- and two-tissue compartment models (1TCM and 2TCM, respectively), along with
multilinear analysis (MA1) and Logan graphical analysis, were performed. Time-stability and test–retest reproducibility of
18F-T-401-PET were also evaluated.
Results 18F-T-401 showed rapid uptake and gradual washout from the brain. Logan graphical analysis showed linearity in
all subjects, indicating reversible radioligand kinetics. Using a metabolite-corrected arterial input function, MA1 estimated
regional total distribution volume (VT) values by best identifability. VT values were highest in the cerebral cortex, moderate
in the thalamus and putamen, and lowest in white matter and the brainstem, which was in agreement with regional MAGL
expression in the human brain. Time-stability analysis showed that MA1 estimated VT values with a minimal bias even using
truncated 60-min scan data. Test–retest reliability was also excellent with the use of MA1.
Conclusions Here, we provide the frst demonstration of in vivo visualization of MAGL in the human brain. 18F-T-401 showed
excellent test–retest reliability, reversible kinetics, and stable estimation of VT values consistent with known regional MAGL
expressions. PET with 18F-T-401-PET is promising tool for measurement of central MAGL.
雑誌名
European Journal of Nuclear Medicine and Molecular Imaging
First‑in‑human in vivo imaging and quantifcation of monoacylglycerol lipase in the brain: a PET study with 18F‑T‑401
