PET Imaging of brain muscarinic receptors with 18F-Fluorobenzyl-Dexetimide: A first in human study

被引:8
|
作者
Rowe, Christopher C. [1 ,2 ]
Krishnadas, Natasha [1 ]
Ackermann, Uwe [1 ]
Dore, Vincent [1 ,3 ]
Goh, Rachel Y. W. [1 ]
Guzman, Rodney [1 ]
Chong, Lee [1 ]
Bozinovski, Svetlana [1 ]
Mulligan, Rachel [1 ]
Kanaan, Richard [4 ]
Dean, Brian [5 ,6 ]
Villemagne, Victor L. [1 ]
机构
[1] Austin Hlth, Dept Mol Imaging & Therapy, Heidelberg, Vic 3084, Australia
[2] Univ Melbourne, Florey Dept Neurosci & Mental Hlth, Parkville, Vic 3070, Australia
[3] CSIRO Hlth & Biosecur, Australian E Hlth Res Ctr, Parkville, Vic 3052, Australia
[4] Univ Melbourne, Dept Psychiat, Austin Hlth, Heidelberg, Vic 3070, Australia
[5] Florey Inst Neurosci & Mental Hlth, Parkville, Vic 3052, Australia
[6] Swinburne Univ, Ctr Mental Hlth, Hawthorn, Vic 3122, Australia
关键词
Positron emission tomography; Muscarinic acetylcholine receptors; Schizophrenia; Neuroreceptor imaging; Fluorine-18; Brain distribution; Radiopharmaceutical; BASAL FOREBRAIN; BIODISTRIBUTION; XANOMELINE; COGNITION; SUBTYPES; BINDING; CORTEX;
D O I
10.1016/j.pscychresns.2021.111354
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
M1 and M4 muscarinic receptor (mAChR) agonists are under development for the treatment of schizophrenia, Alzheimer's and Parkinson's disease. We performed first-in-human PET imaging of mAChR with F-18-Fluorobenzyl-Dexetimide (FDEX) in 10 healthy participants (29.4 +/- 4.3yrs). Four underwent dynamic brain scanning for 240 min, and then six underwent static brain scans at 120 and 160-min post injection of 250 MBq of FDEX. Gjedde-Patlak graphical analysis was applied to determine the influx constant (Ki). Regional tissue ratios (SUVR) were calculated using the cerebellar cortex as the reference region. No adverse events were observed. The tracer showed good brain entry (similar to 4.2% ID at 5 min) but irreversible distribution kinetics over four hours in regions of high mAChR. Binding was consistent with the distribution of mAChR receptors with striatum > cortex > hippocampus >> thalamus >>> cerebellum with low variance in regional binding between subjects. Ki was 0.42 +/- 0.04 in the putamen, 0.27 +/- 0.01 in frontal cortex, 0.25 +/- 0.02 in the hippocampus and 0.10 +/- 0.01 in the thalamus. SUVR at 120 and 240 min. were highly correlated with these Ki values with R-2 of 0.91 and 0.99 respectively. FDEX yields high quality brain images with uptake in the known distribution of mAChR with remarkably little variance between normal subjects.
引用
收藏
页数:7
相关论文
共 50 条
  • [1] In vivo imaging of brain muscarinic receptors with 18F Flurobenzyl Dexetimide: First in human studies
    Rowe, Christopher
    Dean, Brian
    Ackermann, Uwe
    Goh, Rachel
    Guzman, Rodney
    Kanaan, Richard
    Chong, Lee
    Dore, Vincent
    Bozinovski, Svetlana
    Masters, Colin
    Villemagne, Victor
    JOURNAL OF NUCLEAR MEDICINE, 2019, 60
  • [2] PET IMAGING OF BRAIN MUSCARINIC M1 RECEPTORS WITH 18F-FLUROBENZYL DEXETIMIDE: FIRST IN HUMAN STUDIES
    Rowe, C. C.
    Dean, B.
    Ackermann, U.
    Goh, R.
    Guzman, R.
    Kanaan, R.
    Chong, L.
    Dore, V.
    Villemagne, V. L.
    INTERNAL MEDICINE JOURNAL, 2019, 49 : 14 - 14
  • [3] Human biodistribution and internal dosimetry of 4-[18F]fluorobenzyl-dexetimide: a PET radiopharmaceutical for imaging muscarinic acetylcholine receptors in the brain and heart
    Pain, Cameron D.
    O'Keefe, Graeme J.
    Ackermann, Uwe
    Dore, Vincent
    Villemagne, Victor L.
    Rowe, Christopher C.
    EJNMMI RESEARCH, 2020, 10 (01)
  • [4] Human biodistribution and internal dosimetry of 4-[ 18F]fluorobenzyl-dexetimide: a PET radiopharmaceutical for imaging muscarinic acetylcholine receptors in the brain and heart
    Cameron D. Pain
    Graeme J. O’Keefe
    Uwe Ackermann
    Vincent Dore
    Victor L. Villemagne
    Christopher C. Rowe
    EJNMMI Research, 10
  • [5] In vivo imaging of brain estrogen receptors in rats: a [18F]FES PET study
    Khayum, M. A.
    Doorduin, Janine
    Glaudemans, Andor W.
    Dierckx, R. A.
    deVries, Erik F. J.
    EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 2012, 39 : S360 - S361
  • [6] In vivo imaging of brain androgen receptors in rats: a [18F]FDHT PET study
    Khayum, M. A.
    Doorduin, J.
    Antunes, I. F.
    Kwizera, C.
    ZijIma, R.
    den Boer, J. A.
    Dierckx, R. A. J. O.
    de Vries, E. F. J.
    NUCLEAR MEDICINE AND BIOLOGY, 2015, 42 (06) : 561 - 569
  • [7] PET imaging of benzodiazepine receptors in the human brain:: Evaluation of [18F]fluoro-ethylflumazenil.
    Grunder, GM
    Siessmeier, T
    Piel, M
    Schirrmacher, R
    Lange-Asschenfeldt, C
    Vernaleken, I
    Buchholz, HG
    Stoeter, P
    Drzezga, A
    Luddens, H
    Bartenstein, P
    Roesch, F
    JOURNAL OF NUCLEAR MEDICINE, 2000, 41 (05) : 199P - 199P
  • [8] Imaging of receptors in the human brain with PET
    Halldin, C
    PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY, 1996, 65 : SH201 - SH201
  • [9] Correction to: First‑in‑human in vivo imaging and quantification of monoacylglycerol lipase in the brain: a PET study with 18F‑T‑401
    Keisuke Takahata
    Chie Seki
    Yasuyuki Kimura
    Manabu Kubota
    Masanori Ichise
    Yasunori Sano
    Yasuharu Yamamoto
    Kenji Tagai
    Hitoshi Shimada
    Soichiro Kitamura
    Kiwamu Matsuoka
    Hironobu Endo
    Hitoshi Shinotoh
    Kazunori Kawamura
    Ming‑Rong Zhang
    Yuhei Takado
    Makoto Higuchi
    European Journal of Nuclear Medicine and Molecular Imaging, 2022, 49 : 3299 - 3299
  • [10] First-in-human in vivo imaging and quantification of monoacylglycerol lipase in the brain: a PET study with 18F-T-401
    Keisuke Takahata
    Chie Seki
    Yasuyuki Kimura
    Manabu Kubota
    Masanori Ichise
    Yasunori Sano
    Yasuharu Yamamoto
    Kenji Tagai
    Hitoshi Shimada
    Soichiro Kitamura
    Kiwamu Matsuoka
    Hironobu Endo
    Hitoshi Shinotoh
    Kazunori Kawamura
    Ming-Rong Zhang
    Yuhei Takado
    Makoto Higuchi
    European Journal of Nuclear Medicine and Molecular Imaging, 2022, 49 : 3150 - 3161