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PET Measurements of Neuroreceptor Occupancy by Typical and Atypical Neuroleptics

Cleveland Veterans Affairs Medical Center, Cleveland, Ohio
Departments of Radiology and Psychiatry, Case Western Reserve University Medical School and University Hospitals, Cleveland, Ohio
Department of Radiology, Johns Hopkins University Medical School, Baltimore, Maryland

Correspondence: For correspondence or reprints contact: Peter F. Goyer, MD, Chief of Staff, Cleveland VAMC (B), 10,000 Brecksville Rd., Brecksville, OH 44141.

ABSTRACT

The goal of this study was to use PET and ¹¹C-N-methylspiperone (¹¹C-NMSP) to measure the differences in relative occupancy of serotonin (5-hydroxytryptamine-2 or 5-HT_2A) and dopamine-2 (D2) neuroreceptors in subjects being treated with typical or atypical antipsychotic drugs. Methods: We used PET and single-dose ¹¹C-NMSP to measure receptor indices and relative receptor occupancy of 5-HT_2A receptors in frontal cortex and D2 receptors in basal ganglia in five subjects who were neuroleptic free, five subjects who were being treated with typical antipsychotic drugs and five subjects who were being treated with clozapine, an atypical antipsychotic drug. Result: Among the three groups, there were significant differences in 5-HT_2A indices, D2 indices and the ratio of 5-HT_2A to D2 indices. With no overlap, the 5-HT_2A, index separated all subjects who received clozapine and the D2 index separated the remaining two groups. Conclusion: Typical antipsychotic and atypical antipsychotic subjects do have differing patterns of 5-HT_2A and D2 relative receptor occupancy when measured with a single PET scan, single ¹¹C-NMSP radiotracer dose and no separately injected "cold" pharmaceutical.

Key Words: PET • carbon-11-N-methylspiperone • neuroreceptor occupancy

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