Cannabinoid receptors type 2 (CB2R) represent an attractive therapeutic target for neurodegenerative diseases and cancer. Aiming at a positron emission tomography (PET) radiotracer to monitor receptor density and/or occupancy during a CB2R-tailored therapy, we developed here cis-[18F]1-(4-fluorobutyl-N-((1s,4s)-4-methylcyclohexyl)-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxamide ([18F]LU14) starting from the corresponding mesylate precursor. First biological evaluation revealed that [18F]LU14 is a highly affine CB2R radioligand with >80% intact tracer in brain at 30 min p.i. Its further evaluation in a well-established rat model of CB2R overexpression by PET demonstrated its ability to selectively image the CB2R in the brain and its potential as tracer to further investigate diseased related CB2R changes in expression.