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Title: Preclinical evaluation and quantification of [(18)F]MK-9470 as a radioligand for PET imaging of the type 1 cannabinoid receptor in rat brain
Authors: Casteels, Cindy ×
Koole, Michel
Celen, Sofie
Bormans, Guy
Van Laere, Koen #
Issue Date: Sep-2012
Series Title: European journal of nuclear medicine and molecular imaging vol:39 issue:9 pages:1467-1477
Abstract: PURPOSE: [(18)F]MK-9470 is an inverse agonist for the type 1 cannabinoid (CB1) receptor allowing its use in PET imaging. We characterized the kinetics of [(18)F]MK-9470 and evaluated its ability to quantify CB1 receptor availability in the rat brain. METHODS: Dynamic small-animal PET scans with [(18)F]MK-9470 were performed in Wistar rats on a FOCUS-220 system for up to 10 h. Both plasma and perfused brain homogenates were analysed using HPLC to quantify radiometabolites. Displacement and blocking experiments were done using cold MK-9470 and another inverse agonist, SR141716A. The distribution volume (V (T)) of [(18)F]MK-9470 was used as a quantitative measure and compared to the use of brain uptake, expressed as SUV, a simplified method of quantification. RESULTS: The percentage of intact [(18)F]MK-9470 in arterial plasma samples was 80 ± 23 % at 10 min, 38 ± 30 % at 40 min and 13 ± 14 % at 210 min. A polar radiometabolite fraction was detected in plasma and brain tissue. The brain radiometabolite concentration was uniform across the whole brain. Displacement and pretreatment studies showed that 56 % of the tracer binding was specific and reversible. V (T) values obtained with a one-tissue compartment model plus constrained radiometabolite input had good identifiability (≤10 %). Ignoring the radiometabolite contribution using a one-tissue compartment model alone, i.e. without constrained radiometabolite input, overestimated the [(18)F]MK-9470 V (T), but was correlated. A correlation between [(18)F]MK-9470 V (T) and SUV in the brain was also found (R (2) = 0.26-0.33; p ≤ 0.03). CONCLUSION: While the presence of a brain-penetrating radiometabolite fraction complicates the quantification of [(18)F]MK-9470 in the rat brain, its tracer kinetics can be modelled using a one-tissue compartment model with and without constrained radiometabolite input.
URI: 
ISSN: 1619-7070
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Radiopharmacy
Nuclear Medicine & Molecular Imaging
× corresponding author
# (joint) last author

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