Dihydrotetrabenazine positron emission tomography imaging in early, untreated Parkinson's disease.
OBJECTIVE
To determine the sensitivity of positron emission tomography with 11C-labeled dihydrotetrabenazine (DTBZ) to the nigrostriatal changes associated with early, untreated Parkinson's disease (PD), and to determine the correlation between any regionally reduced DTBZ binding and the major motor features of PD.


METHODS
Untreated patients with early PD (n = 27) and age-matched control subjects (n = 33) underwent DTBZ/positron emission tomography scanning to measure binding to the presynaptic type 2 vesicular monoamine transporter site in dopaminergic neurons in basal ganglia regions. Clinical symptoms were rated with the Unified Parkinson's Disease Rating Scale.


RESULTS
Mean striatal DTBZ binding values in the patient group were decreased as compared with control subjects (p < 0.001) in all regions examined. The difference between patients and control subjects was most marked in the midputamen, where only one patient had DTBZ binding within 3 standard deviations of the control mean. Bradykinesia and rigidity scores correlated with DTBZ binding in the contralateral midputamen region, particularly for the clinically least affected limbs. Tremor scores showed no significant correlation.


CONCLUSIONS
Reduced striatal binding of DTBZ is associated with early PD. Tremor appears to be only partially related to presynaptic dopaminergic function and may have a mechanism differing from that of symptoms such as bradykinesia. The method appears to be most sensitive in mildly affected individuals with a possible "floor" effect that may limit the degree of additional change occurring once more severe clinical symptoms are evident.
Martin
W R Wayne
WR
Division of Neurology, University of Alberta, Edmonton, Alberta. wayne.martin@ualberta.ca
Wieler
Marguerite
M
Stoessl
A Jon
AJ
Schulzer
Michael
M
D000328:Adult; D000368:Aged; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D003430:Cross-Sectional Studies; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000175:diagnosis* / Q000000981:diagnostic imaging* / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding / Q000502:physiology; D013747:Tetrabenazine / Q000031:analogs & derivatives* / Q000378:metabolism
C032811:dihydrotetrabenazine; D013747:Tetrabenazine