RT Journal Article
SR Electronic
T1 Dopamine Transporter Concentration Is Reduced in Asymptomatic Machado-Joseph Disease Gene Carriers
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 153
OP 159
VO 43
IS 2
A1 Tzu-Chen Yen
A1 Kai-Yuan Tzen
A1 Min-Chi Chen
A1 Yah-Huei Wu Chou
A1 Rou-Shayn Chen
A1 Chi-Jen Chen
A1 Shiaw-Pyng Wey
A1 Gann Ting
A1 Chin-Song Lu
YR 2002
UL http://jnm.snmjournals.org/content/43/2/153.abstract
AB Dopamine transporter (DAT) binding is decreased in Machado-Joseph disease (MJD) patients. To further investigate the DAT activity in asymptomatic MJD (aMJD) gene carriers, we performed this prospective study using 99mTc-TRODAT-1 ([99mTc][2[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]-methyl](2-mercaptoethyl)amino]ethyl]amino]ethane-thiolato(3-)-N2,N2′,S2,S2]oxo-[1R-(exo-exo)])) brain SPECT on 5 aMJD gene carriers, 10 age-matched MJD patients, and 10 age-matched healthy control subjects. Methods: Brain SPECT images were acquired 4 h after intravenous injection of 925 MBq (25 mCi) 99mTc-T RODAT-1, which is known to bind specifically to the DAT on the nigrostriatal terminals. By fusing these SPECT images with a striatal atlas, obtained from MRI, binding of this tracer in the entire striatum was measured and the uptake values in bilateral striatal areas were compared between these 3 groups. Results: The uptake values of the aMJD gene carriers (P < 0.001) and MJD patients (P < 0.001) displayed a significant reduction compared with those of the control subjects. The reduction was more severe in the MJD patient group (P < 0.05). Bilateral putamen-to-caudate ratios were significantly lower in the aMJD gene carrier and MJD patient groups (P < 0.001). The dopamine neuronal activity, as represented by the tracer binding, was more prominently affected in the putamen in these patients and gene carriers. Conclusion: 99mTc-TRODAT-1 brain SPECT is capable of detecting early alteration of dopamine neurons in the striatal region. Significantly, the results suggest that this impairment of presynaptic dopamine function actually occurs at an early stage, which was previously unrecognized in these aMJD gene carriers.