Title: [18F]MK-9470, a positron emission tomography (PET) tracer for in vivo human PET brain imaging of the cannabinoid-1 receptor
Authors: Burns, H Donald ×
Van Laere, Koen
Sanabria-Bohórquez, Sandra
Hamill, Terence G
Bormans, Guy
Eng, Wai-si
Gibson, Ray
Ryan, Christine
Connolly, Brett
Patel, Shil
Krause, Stephen
Vanko, Amy
Van Hecken, Anne
Dupont, Patrick
De Lepeleire, Inge
Rothenberg, Paul
Stoch, S Aubrey
Cote, Josee
Hagmann, William K
Jewell, James P
Lin, Linus S
Liu, Ping
Goulet, Mark T
Gottesdiener, Keith
Wagner, John A
de Hoon, Jan
Mortelmans, Luc
Fong, Tung M
Hargreaves, Richard J #
Issue Date: Jun-2007
Series Title: Proceedings of the National Academy of Sciences of the United States of America vol:104 issue:23 pages:9800-9805
Abstract: [(18)F]MK-9470 is a selective, high-affinity, inverse agonist (human IC(50), 0.7 nM) for the cannabinoid CB1 receptor (CB1R) that has been developed for use in human brain imaging. Autoradiographic studies in rhesus monkey brain showed that [(18)F]MK-9470 binding is aligned with the reported distribution of CB1 receptors with high specific binding in the cerebral cortex, cerebellum, caudate/putamen, globus pallidus, substantia nigra, and hippocampus. Positron emission tomography (PET) imaging studies in rhesus monkeys showed high brain uptake and a distribution pattern generally consistent with that seen in the autoradiographic studies. Uptake was blocked by pretreatment with a potent CB1 inverse agonist, MK-0364. The ratio of total to nonspecific binding in putamen was 4-5:1, indicative of a strong specific signal that was confirmed to be reversible via displacement studies with MK-0364. Baseline PET imaging studies in human research subject demonstrated behavior of [(18)F]MK-9470 very similar to that seen in monkeys, with very good test-retest variability (7%). Proof of concept studies in healthy young male human subjects showed that MK-0364, given orally, produced a dose-related reduction in [(18)F]MK-9470 binding reflecting CB1R receptor occupancy by the drug. Thus, [(18)F]MK-9470 has the potential to be a valuable, noninvasive research tool for the in vivo study of CB1R biology and pharmacology in a variety of neuropsychiatric disorders in humans. In addition, it allows demonstration of target engagement and noninvasive dose-occupancy studies to aid in dose selection for clinical trials of CB1R inverse agonists.
ISSN: 0027-8424
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Nuclear Medicine & Molecular Imaging
Radiopharmaceutical Research
Clinical Pharmacology Centre (-)
Research Group Experimental Neurology
Laboratory for Cognitive Neurology
× corresponding author
# (joint) last author

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