SPECT imaging of pre- and postsynaptic dopaminergic alterations in L-dopa-untreated PD

Background In PD, presynaptic dopamine transporters are known to be decreased, whereas postsynaptic striatal D2 receptors are proposed to be upregulated. However, the relationship between these alterations is not clear. Objective: To evaluate the ability of SPECT to detect both the pre- and postsynaptic dopaminergic alterations of the striatum in patients with L-dopa-untreated PD, Methods: We studied 10 L-dopa-untreated patients with clinically mild PD and 21 age-matched normal controls. Individuals had both presynaptic [T-123]beta-CIT dopamine transporter and postsynaptic [I-123]IBF D2 SPECT studies 1 week apart. Results: In PD patients, the dopamine transporter binding potential Rv ipsilateral/contralateral to the most affected limbs was 30%/41%, 41%/50%, and 59%68% lower than controls for caudate, anterior putamen, and posterior putamen, respectively. These bilateral Re decreases showed a lateralized difference more reduced in the contralateral striatum as well as intrastriatal differences most reduced in the posterior putamen. In contrast, in PD patients the D2 binding potential Rv psilateral/contralateral was 15%/16% higher for caudate, 18%/14% higher for anterior putamen, and 28%/31% higher for posterior putamen. These bilateral Re increases showed no lateralized differences and less marked intrastriatal differences. The motor Unified Parkinson's Disease Rating Scale scores negatively correlated with dopamine transporter Rv but not with D2 Rv. Conclusions: SPECT imaging can detect characteristic dopaminergic alterations in the striatum of dopa-untreated PD patients including the upregulation of postsynaptic D2 receptors (denervation supersensitivity). SPECT is widely available and is a promising clinical tool to evaluate PD patients.