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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 D₂ receptor selectivity as the mechanism of action of clozapine. METHOD: Positron emission tomography (PET) was used to examine extrastriatal as well as striatal dopamine D₂ receptor occupancy in four patients treated with clozapine and three patients treated with haloperidol. The reference radioligand [¹¹C]raclopride was used for determination of D₂ receptor occupancy in the striatum. The radioligand [¹¹C]FLB 457 was chosen for determination of D₂ receptor occupancy in the thalamus, the temporal cortex, and the frontal cortex. RESULTS: In patients treated with haloperidol the D₂ receptor occupancy was high in all examined brain regions. In clozapine-treated patients the D₂ 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.

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