Within-subject comparison of striatal D2 receptor occupancy measurements using 123I-IBZM SPECT and 11C-raclopride PET

Abstract

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Objectives: Reported literature values of D2 receptor occupancy (D2RO) achieved by antipsychotic drugs tend to be lower when measured with SPECT and 123I-IBZM than with PET and 11C-Raclopride. To clarify this issue, D2RO was measured in the same subjects using both 123I-IBZM SPECT and 11C-Raclopride PET.

Methods: Twenty schizophrenic patients on antipsychotic (AP) monotherapy with risperidone (n= 7; 3-9mg/d), olanzapine (n=5;5-20mg/d) or clozapine (n=8;150-450mg/d) at stable doses, and ten healthy volunteers (HV) underwent both a 123I-IBZM SPECT and a 11C-Raclopride PET in random order on different days within a week, at the same time after last AP dose administration. For quantification, the tissue ratio method at pseudo-equilibrium and the specific uptake ratios (SUR) were used for SPECT, and simplified reference tissue model and binding potential (BP) were used for PET. Analysis was performed using the cerebellum as reference region for both techniques. D2RO was measured as the percentage of change from the mean SUR and BP of HV.

Results: SPECT/PET measured D2RO ranged 6.78-100.63% /19.74-87.83%. Correlations showed a D2RO SPECT underestimation of 13.8% (RO_SPECT=0.86×RO_PET, R²=0.45). Within-subject AP plasma levels did not differ between the PET and SPECT days.

Conclusions: This study confirms that there is a 123I-IBZM SPECT underestimation of striatal D2RO measurements compared to 11C-Raclopride PET. This fact should be taken into account when interpreting PET and SPECT D2RO results.