Decreased dopamine transporter binding in Machado-Joseph disease.
The aim of this study was to use 99mTc-TRODAT-1 brain SPECT for investigation of the binding of dopamine transporter (DAT) in the nigrostriatal dopaminergic pathway of symptomatic Machado-Joseph disease (MJD) and to compare the results with the abnormal cytidylate, adenylate, and guanylate (CAG) expansion in the MJD1 gene and other clinical factors.


METHODS
Ten symptomatic MJD patients (8 women, 2 men; age range, 20-71 y; mean age +/- SD, 36.4 +/- 10.6 y; mean duration of illness, 9.8 +/- 5.4 y) and 21 healthy volunteers (age range, 24-71 y; mean age, 47.6 +/- 20.1 y) were examined. Brain SPECT images were acquired 4 h after injection. The ratio of specific to nonspecific nigrostriatal 99mTc-TRODAT-1 binding was measured and compared with the clinical symptoms, duration of illness, and size of abnormal expanded CAG repeats.


RESULTS
All nigrostriatal 99mTc-TRODAT-1 ratios were significantly lower in MJD patients than in healthy volunteers (P < 0.05). Discriminant function analysis of all MJD patients showed that the decreased binding of 99mTc-TRODAT-1 in the putamen was not significantly different from that in the caudate nucleus. Eight of 10 MJD patients had significantly decreased 99mTc-TRODAT-1 uptake. Of these 8, 2 had extrapyramidal signs and 6 had no obvious extrapyramidal signs. The other 2 patients, who had normal 99mTc-TRODAT-1 uptake, had no obvious extrapyramidal signs.


CONCLUSIONS
Our findings indicate that 99mTc-TRODAT-1 brain SPECT is an appropriate method for evaluating damage to the nigrostriatal DAT in symptomatic MJD patients with and without extrapyramidal signs. The decreased binding of 99mTc-TRODAT-1 in the nigrostriatal dopaminergic pathway in symptomatic MJD patients correlates with the phenotype of extrapyramidal signs but not with the abnormal CAG repeat length, age at disease onset, or disease duration.
Yen
T C
TC
Department of Nuclear Medicine, Chang Gung Memorial Hospital, Taipei Medical Center and School of Medicine, Chang Gung University, Taiwan.
Lu
C S
CS
Tzen
K Y
KY
Wey
S P
SP
Chou
Y H
YH
Weng
Y H
YH
Kao
P F
PF
Ting
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000378:metabolism; D002648:Child; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D006801:Humans; D017827:Machado-Joseph Disease / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D015609:Organotechnetium Compounds; D011699:Putamen / Q000000981:diagnostic imaging / Q000378:metabolism; D013378:Substantia Nigra / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon; D019680:Trinucleotide Repeat Expansion; D014326:Tropanes
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D015609:Organotechnetium Compounds; C493214:SLC6A3 protein, human; D014326:Tropanes; C104196:technetium Tc 99m TRODAT-1; D004298:Dopamine