raclopride and Multiple-System-Atrophy

Striatal dopamine D(2) receptor (D2R) PET has been proposed to differentiate between Parkinson disease (PD) and multiple-system atrophy with predominant parkinsonism (MSA-P). However, considerable overlap in striatal D(2) binding may exist between PD and MSA-P. It has been shown that imaging of neuronal activity, as determined by metabolism or perfusion, can also help distinguish PD from MSA-P. We investigated whether the differential diagnostic value of (11)C-raclopride PET could be improved by dynamic scan analysis combining D2R binding and regional tracer influx.. (11)C-raclopride PET was performed in 9 MSA-P patients (mean age +/- SD, 56.2 +/- 10.2 y; disease duration, 2.9 +/- 0.8 y; median Hoehn-Yahr score, 3), 10 PD patients (mean age +/- SD, 65.7 +/- 8.1 y; disease duration, 3.3 +/- 1.5 y; median Hoehn-Yahr score, 1.5), and 10 healthy controls (mean age +/- SD, 61.6 +/- 6.5 y). Diagnosis was obtained after prolonged follow-up (MSA-P, 5.5 +/- 2.0 y; PD, 6.0 +/- 2.3 y) using validated clinical criteria. Spatially normalized parametric images of binding potential (BP) and local influx ratio (R(1) = K(1)/K'(1)) of (11)C-raclopride were obtained using a voxelwise reference tissue model with occipital cortex as reference region. Stepwise forward discriminant analysis with cross-validation, with and without the inclusion of regional R(1) values, was performed using a predefined volume-of-interest template.. Using conventional BP values, we correctly classified 65.5% (all values given with cross-validation) of 29 cases only. The combination of BP and R(1) information increased discrimination accuracy to 79.3%. When healthy controls were not included and patients only were considered, BP information alone discriminated PD and MSA-P in 84.2% of cases, but the combination with R(1) data increased accuracy to 100%.. Discriminant analysis using combined striatal D2R BP and cerebral influx ratio information of a single dynamic (11)C-raclopride PET scan distinguishes MSA-P and PD patients with high accuracy and is superior to conventional methods of striatal D2R binding analysis.

Topics: Aged; Biological Transport; Case-Control Studies; Cerebrovascular Circulation; Diagnosis, Differential; Discriminant Analysis; Early Diagnosis; Female; Humans; Male; Middle Aged; Multiple System Atrophy; Neostriatum; Parkinson Disease; Positron-Emission Tomography; Raclopride

We used PET with the tracers [18F]fluorodeoxyglucose (FDG), [18F]fluorodopa (FDOPA) and [11C]raclopride (RACLO) to study striatal glucose and dopa metabolism, and dopamine D2 receptor binding, respectively, in nine patients with multiple system atrophy. Ten patients with classical Parkinson's disease were investigated with the same three PET tracers' and three separate groups, each of 10 healthy subjects, served as control populations. We found that striatal FDOPA values separated all healthy subjects from patients with parkinsonism but they were not useful in distinguishing multiple system atrophy from Parkinson's disease. Conversely, striatal RACLO as well as FDG values discriminated all multiple system atrophy from Parkinson's disease patients as well as from healthy control subjects. Metabolic and receptor binding decrements in the putamen of multiple system atrophy patients were significantly correlated. Stepwise regression analysis revealed that a linear combination of putamen RACLO and FDOPA values accurately predicted clinical measures of disease severity in the multiple system atrophy group. Our findings suggest that striatal FDG and particularly RACLO are sensitive and effective measures of striatal function and may help characterizing patients with multiple system atrophy. In contrast, FDOPA measurements are accurate in detecting abnormalities of the nigrostriatal dopaminergic system but may not distinguish among different forms of parkinsonism.

Topics: Aged; Carbon Radioisotopes; Caudate Nucleus; Corpus Striatum; Diagnosis, Differential; Dihydroxyphenylalanine; Female; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Humans; Hypotension, Orthostatic; Male; Middle Aged; Multiple System Atrophy; Neurons; Parkinson Disease; Putamen; Raclopride; Radiography; Radiopharmaceuticals; Receptors, Dopamine D2; Regression Analysis; Salicylamides; Tomography, Emission-Computed