Does combined imaging of the pre- and postsynaptic dopaminergic system increase the diagnostic accuracy in the differential diagnosis of parkinsonism?

We hypothesized that combining pre- and postsynaptic quantitative information about the dopaminergic system would provide a higher diagnostic accuracy in the differential diagnosis of parkinsonism than specific striatal D(2) receptor binding alone. Therefore, the aim of the study was to introduce new semi-quantitative parameters and evaluate their ability to discriminate between Parkinson's disease (IPS) and non-idiopathic parkinsonian syndromes (non-IPS). In 100 patients (69 IPS, 31 non-IPS), postsynaptic [(123)I]IBZM and presynaptic [(123)I]FP-CIT SPECT scans were evaluated by observer-independent techniques. The diagnostic performances of striatal dopamine transporter (DAT) and D(2) receptor binding, their respective asymmetries, and a combination of pre- and postsynaptic asymmetry were evaluated with ROC analyses. A logistic regression model was generated combining factors to calculate the probability for each patient of belonging to either diagnostic group. D(2) receptor binding provided a sensitivity of 87.1% and a specificity of 72.5% with an area under the curve (AUC) of 0.866. The AUCs of other single parameters were lower than that of D(2) binding. A gain of diagnostic power (p = 0.026) was reached with a model combining pre- and postsynaptic asymmetries and D(2) binding (sensitivity 90.3%, specificity 73.9%, AUC 0.893). The combination of quantitative parameters of presynaptic DAT and postsynaptic D(2) receptor binding demonstrates superior diagnostic power in the differentiation of patients with IPS and non-IPS than the established approach based on D(2) binding alone. Striatal D(2) receptor binding and the combination of DAT and IBZM binding asymmetries are the factors contributing most in separating these diagnostic groups.