Positron emission tomography (PET) measurements of striatal D(2) receptors in untreated Parkinson's disease patients with follow-up after 6 and 12 months' treatment with SINEMET((R)) or SINEMET((R)) CR.
Untreated Parkinson's disease (FD) patients typically demonstrate an upregulation in striatal D(2) receptor binding. Reduced D(2) binding is found in levodopa-treated patients with a fluctuating response to this drug. Using PET and (11)C-raclopride, we determined striatal:background uptake ratios to provide a measure of D(2) receptor binding in 10 untreated, newly diagnosed PD patients who were treated subsequently with levodopa for 1 yr. At baseline, we found increased striatal D(2) receptor uptake ratios in patients (3.89) in comparison to normal controls (3.22; p < 0.02). Furthermore, the ratio between caudate and putamen D(2) 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((R)) (300 mg of levodopa/d) or SINEMET((R)) 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 post-treatment 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 D(2) 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 D(2) receptor downregulation occurs.
Uitti
R J
RJ
Neurodegenerative Disorders Centre, Vancouver Hospital and Health Sciences Centre, University of British Columbia, Vancouver, British Columbia, Canada; Mayo Clinic Jacksonville, Department of Neurology, Jacksonville, FL, U.S.A.
Vingerhoets
F J
FJ
Hayward
M
M
Cooper
S
S
Snow
B J
BJ