IBZM SPECT measurement of D2 receptor occupancy by haloperidol and risperidone

This study was undertaken to determine if 1-123 IBZM SPECT could be utilized to determine relationships between D2 receptor occupancy and dosage or serum concentration of neuroleptic drugs. Five schizophrenic patients were studied after three weeks of treatment with haloperidol; three of these patients underwent a second study after three weeks of treatment on a different dose. Six schizophrenic patients were studied during risperidone treatment, four of whom underwent a second study. All scans were treated as independent measurements. On the day of the SPECT scans, the clinical state of the patients was rated independently by two psychiatrists and blood levels of neuroleptic drugs were obtained. Equilibrium binding of IBZM was estimated by determining the ratio of specific (basal gangliacerebellum) to nonspecific (cerebellum) binding during a 30 minute scan, obtained 90 minutes after injection. The same measure was obtained from 16 normal controls. D2 receptor occupancy was estimated with the following formula: [1 - (patient value/normal mean)] × 100. The relationship between neuroleptic dose or blood level and D2 occupancy was estimated by fitting the following two-parameter hyperbolic function to the observed data: occupancy =(α*x)/(β+x), where α = an estimate of maximal occupancy, x = neuroleptic dose (mg/kg) or blood level (ng/ml), and β = constant for drug inhibition as expressed by serum concentration. The predicted maximal occupancy was 82.9% and the coefficient of determination of the curve fit was R2 =0.87 when the relationship between serum concentration of haloperidol and occupancy was examined. For haloperidol dosage, the predicted maximal occupancy was 63.8% (R2 =0.80). For parent risperidone serum concentration, the predicted maximai occupancy was 73.1% (R2 =0.39). Results obtained with 9-OH-risperidone, and total risperidone serum concentrations were iess reliable. For risperidone dosage, the predicted maximal occupancy was 62.0% (R2 =0 50). scans obtained from patients on haloperidol were associated with clinically apparent parkinsonism, while this was true in only scans obtained on risperidone. These preliminary data suggest that there is a more predictable relationship between haloperidol dose or serum level with D2 occupancy than that observed with risperidone. Also, at similar degrees of D2 occupancy, haloperidol treatment is more likely to be associated with parkinsonism than is risperidone.