Positron emission tomography (PET) measurements of striatal D₂ receptors in untreated Parkinson's disease patients with follow-up after 6 and 12 months' treatment with SINEMET® or SINEMET® CR

Untreated Parkinson's disease (PD) patients typically demonstrate an upregulation in striatal D₂ receptor binding. Reduced D₂ binding is found in levodopa-treated patients with a fluctuating response to this drug. Using PET and ¹¹C-raclopride, we determined striatal:background uptake ratios to provide a measure of D₂ receptor binding in 10 untreated, newly diagnosed PD patients who were treated subsequently with levodopa for 1 yr. At baseline, we found increased striatal D₂ receptor uptake ratios in patients (3.89) in comparison to normal controls (3.22; p < 0.02). Furthermore, the ratio between caudate and putamen D₂ uptake was significantly reduced in patients (0.86 vs. 0.98 in normals, p < 0.01). Patients were subsequently randomized to treatment with either SINEMET® (300 mg of levodopa/d) or SINEMET® CR (400 mg of levodopa/d). Patients in both groups received similar symptomatic benefit following treatment, and none developed motor fluctuations. All patients were rescanned after 6 months of treatment. There were no significant differences in striatal (or caudate and putamen considered singly) raclopride binding between the first and 6 month post-treatment scans. Similarly, there were no significant differences between pre- and 6 month posttreatment scans on the basis of levodopa preparations. Patients were subsequently treated with the other Sinemet preparation for another 6 month period before rescanning. Again, no differences in raclopride binding were found compared to pre-treatment or between type of levodopa preparation. We conclude that there is no evidence for downregulation of D₂ receptor binding after 1 yr of low-dose levodopa therapy in patients who receive symptomatic benefit without motor fluctuations, regardless of type of preparation. Follow-up of such individuals may permit determination of when and in what context D₂ receptor downregulation occurs.