Because CNS neuroleptic concentration cannot be directly measured in
patients, the relation between clinical response and extent of dopamine
receptor blockade is unknown. This relationship is critical in ascertaining
whether nonresponse to neuroleptics is the result merely of inadequate CNS
drug levels or of more basic biological differences in pathophysiology.
Using [18F]N-methylspiroperidol and positron emission tomography, the
authors assessed dopamine receptor occupancy in 10 schizophrenic patients
before and after treatment with haloperidol. Responders and nonresponders
had virtually identical indices of [18F]N-methylspiroperidol uptake after
treatment, indicating that failure to respond clinically was not a function
of neuroleptic uptake or binding in the CNS.