@article{oai:repo.qst.go.jp:00084537,
 author = {Keisuke, Takahata and Chie, Seki and Yasuyuki, Kimura and Manabu, Kubota and Masanori, Ichise and Yasunori, Sano and Yamamoto, Yasuharu and Kenji, Tagai and Hitoshi, Shimada and Soichiro, Kitamura and Kiwamu, Matsuoka and Hironobu, Endo and Hitoshi, Shinoto and Kazunori, Kawamura and Zhang, Ming-Rong and Yuhei, Takado and Makoto, Higuchi and Keisuke, Takahata and Chie, Seki and Yasuyuki, Kimura and Manabu, Kubota and Masanori, Ichise and Yasunori, Sano and Yamamoto, Yasuharu and Kenji, Tagai and Hitoshi, Shimada and Soichiro, Kitamura and Kiwamu, Matsuoka and Hironobu, Endo and Hitoshi, Shinoto and Kazunori, Kawamura and Zhang, Ming-Rong and Yuhei, Takado and Makoto, Higuchi},
 journal = {European Journal of Nuclear Medicine and Molecular Imaging},
 month = {Jan},
 note = {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.},
 pages = {3150--3161},
 title = {First‑in‑human in vivo imaging and quantifcation  of monoacylglycerol lipase in the brain: a PET study with 18F‑T‑401},
 volume = {49},
 year = {2022}
}