No support for regional selectivity in clozapine-treated patients:: A PET study with [11C]raclopride and [11C]FLB 457

Objective: The authors' goal was to test the hypothesis of extrastriatal D-2 receptor selectivity as the mechanism of action of clozapine. Method: Positron emission tomography (PET) was used to examine extrastriatal as well as striatal dopamine D-2 receptor occupancy in four patients treated with clozapine and three patients treated with haloperidol. The reference radioligand [C-11]raclopride was used for determination of D-2 receptor occupancy in the striatum. The radioligand [C-11]FLB 457 was chosen for determination of D-2 receptor occupancy in the thalamus, the temporal cortex. and the frontal. Results: In patients treated with haloperidol the D-2 receptor occupancy was high in all examined brain regions. In clozapine-treated patients the D-2 receptor occupancy was relatively low in both the striatum and the extrastriatal regions. Conclusions: The results from the present study give no support for the hypothesis of regional selectivity as the mechanism of action for clozapine.