[¹⁸F]Fallypride PET assessment of D₂/D₃ receptor binding in schizophrenia

Abstract

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Objectives: Alterations in dopamine (DA) D₂/D₃ receptor binding have been implicated in schizophrenia, and a meta-analysis of receptor imaging studies has shown a modest elevation in striatum. New radioligands have more recently allowed the assessment of these receptors in extrastriatal regions. The goal of this study was to evaluate binding of [¹⁸F]fallypride to these receptors in both striatal and extrastriatal regions in schizophrenia.

Methods: Sixteen patients with schizophrenia and 22 group-matched healthy controls were scanned with an HR+ camera. Each scan was acquired over 240 min in 3 sessions of 50, 60 and 40 min with breaks. Arterial blood was collected for metabolite corrected plasma input function. Regions of interest were drawn on each subject’s MRI and transferred to the coregistered PET. Data were analyzed by 2 tissue compartment modeling and binding potential BP_ND was compared with 2-tailed t tests.

Results: Mean regional BP_ND values were slightly elevated in striatum in schizophrenia as in prior literature. However, no striatal or extrastriatal region showed significantly altered BP_ND. For example, mean regional BP_ND values in patients and controls respectively were 20.2 ± 4.2 and 19.5 ± 2.9 in whole striatum, 18.8 ± 4.1 and 18.3 ± 3.1 in dorsal caudate, 1.9 ± 0.4 and 2.0 ± 0.4 in amygdala, and 2.2 ± 0.5 and 2.1 ± 0.3 in thalamus (p > .05 in all cases).

Conclusions: In this study, we did not find significant alterations in D₂/D₃ receptor expression levels in schizophrenia. Our observations are consistent with some but not all previous studies of extrastriatal D₂/D₃ receptors. Assessing DA levels may be a more productive approach to understanding the pathophysiology of the illness as previously shown for the striatum.

Research Support: NIMH