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.