Title: Synthesis, in vitro and in vivo evaluation of fluorine-18 labelled FE-GW405833 as a PET tracer for type 2 cannabinoid receptor imaging
Authors: Evens, Nele
Vandeputte, Caroline
Muccioli, Giulio G
Lambert, Didier M
Baekelandt, Veerle
Verbruggen, Alfons
Debyser, Zeger
Van Laere, Koen
Bormans, Guy # ×
Issue Date: Aug-2011
Publisher: Pergamon
Series Title: Bioorganic & Medicinal Chemistry vol:19 issue:15 pages:4499-4505
Abstract: The type 2 cannabinoid receptor (CB(2)R) is part of the endocannabinoid system and is expressed in tissues related to the immune system. As the CB(2)R has a very low brain expression in non-pathological conditions, but is upregulated in activated microglia, it is an interesting target for visualization of neuroinflammation using positron emission tomography with a suitable radiolabeled CB(2)R ligand. In this study, we radiolabelled a fluoroethyl derivative of GW405833, a well known CB(2)R partial agonist, with fluorine-18 (half-life 109.8min) by alkylation of the phenol precursor with 1-bromo-2-[(18)F]fluoroethane. In vitro studies showed that FE-GW405833 behaved as a selective high affinity (27nM) inverse agonist for hCB(2)R. [(18)F]FE-GW405833 showed moderate initial brain uptake in mice and rats, but a slow washout from brain and plasma due to retention of a radiometabolite. Specific binding of the tracer to human CB(2)R was demonstrated in vivo in a rat model with local CB(2)R overexpression in the brain. Optimized derivatives of GW405833 that are less susceptible to metabolism will need to be developed in order to provide a useful tracer for CB(2)R quantification with PET.
ISSN: 0968-0896
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Virology and Gene Therapy
Nuclear Medicine & Molecular Imaging
Research Group for Neurobiology and Gene Therapy
× corresponding author
# (joint) last author

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