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

Psychiatry CPDM, GlaxoSmithKline, Barcelona, Spain.
NeuroImage (Impact Factor: 6.36). 03/2009; 46(2):447-58. DOI: 10.1016/j.neuroimage.2009.02.005
Source: PubMed


Antipsychotic-induced D2 receptor occupancy values tend to be lower when measured with [(123)I]IBZM SPECT than with [(11)C]Raclopride PET. To clarify this issue, D2 receptor occupancy was measured in the same subjects using both techniques. Twenty patients with schizophrenia on monotherapy with risperidone (n=7; 3-9 mg/d), olanzapine (n=5; 5-20 mg/d) or clozapine (n=8; 150-450 mg/d) at stable doses, and ten healthy volunteers (HV) underwent both a [(123)I]IBZM SPECT and a [(11)C]Raclopride PET examinations in random order on different days within a week. Patients with schizophrenia were scanned at a fixed interval after last dose administration. Quantification of receptor availability was performed using the most conventional methods from the literature: the tissue ratio derived specific uptake ratios (SUR) were used for SPECT, and simplified reference tissue model (SRTM) derived binding potentials (BP(ND)) for PET. Analysis was performed using both occipital cortex and cerebellum as reference regions for both modalities. Striatal D2 receptor occupancy was measured as the percentage reduction of [(123)I]IBZM SUR or [(11)C]Raclopride BP(ND) compared to the population average measured in HV using the same modality. Occupancy values measured by SPECT were lower than those measured with PET, by 12.4% and 13.8% when occipital cortex and cerebellum were used as reference regions. This difference should be taken in consideration when interpreting reported antipsychotic striatal D2 receptor occupancy values from the literature.

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    • "Although the specific reasons for such gradual evolution in dosage patterns are not clear, clinical trials may include subjects with somewhat less diagnostic heterogeneity, comorbidity and illness severity than patients encountered in clinical practice settings (Seeman, 2001). In addition, since D 2 receptor occupancy rates show a significant degree of inter-individual variability at a given dose (Kapur et al., 2000; Mamo et al., 2004; Catafau et al., 2009), higher daily doses may be required in some patients to ensure that adequate steady-state plasma and CNS concentrations are reached. From a practical standpoint, dose escalation is one of the most frequently used treatment strategies for patients with more severe illness and those who do not respond to initial treatment at lower therapeutic doses (Kinon et al., 2004; Schwartz and Stahl, 2011). "
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    Schizophrenia Research 04/2013; 145(s 1–3):101–109. DOI:10.1016/j.schres.2013.01.009 · 3.92 Impact Factor
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    • "Involvement of 5-HT 2A and mGlu 2 in schizophrenia Dopamine, glutamate and serotonin are the three major neurotransmitters playing a role in the pathophysiology/treatment of schizophrenia. Almost all marketed antipsychotic drugs are potent dopamine D 2 receptor antagonists and increased striatal dopamine release is observed in medication-free first-break or relapsing schizophrenic patients (Carlsson and Lindqvist, 1963; Catafau et al., 2009; Creese et al., 1976; Howes et al., 2012; Seeman et al., 1976). "
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Santiago Bullich