Test-retest reliability of central [11C]raclopride binding at high D2 receptor occupancy. A PET study in haloperidol-treated patients.
Central D2 dopamine receptor occupancy may be a useful measure to establish clinical guidelines for optimal antipsychotic drug treatment. The use of positron emission tomography (PET) to explore quantitative relationships among D2 receptor occupancy and clinical effects depends on the reliability of such measurements. The calculation of D2 receptor occupancy using [11C]raclopride is routinely based on a ratio-equilibrium analysis, in which the ratio of radioactivity concentration in the striatum to that in the cerebellum is determined. To examine the reliability of such ratios, a test-retest analysis was performed in four schizophrenic patients treated with haloperidol decanoate. PET experiments with [11C]raclopride were repeated in each subject during the same day. The putamen to cerebellum ratio (P/C ratio) ranged from 1.44 to 1.07 among the four patients, corresponding to a D2 receptor occupancy of 62 to 71%. In each subject, the P/C ratios remained highly similar, with quotients 0.98, 1.01, 1.04 and 1.06 between the two experiments. The high test-retest reproducibility of the P/C ratios indicates that measurements of D2 receptor occupancy with the present methods are highly reliable, and support the further use of PET to optimize the drug treatment of schizophrenia.
Karolinska Institute, Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden. svanten@syk.ks.se
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Nyberg
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Farde
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Halldin
D000328:Adult; D014150:Antipsychotic Agents / Q000493:pharmacokinetics*; D001665:Binding Sites; D002531:Cerebellum / Q000000981:diagnostic imaging* / Q000378:metabolism*; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006220:Haloperidol / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D011699:Putamen / Q000000981:diagnostic imaging* / Q000378:metabolism*; D020891:Raclopride; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D015203:Reproducibility of Results; D012457:Salicylamides / Q000493:pharmacokinetics*; D012559:Schizophrenia / Q000188:drug therapy*; D014055:Tomography, Emission-Computed
D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D020891:Raclopride; D006220:Haloperidol