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Dopamine transporter concentration is reduced in asymptomatic Machado-Joseph disease gene carriers
Tzu-Chen Yen1, Kai-Yuan Tzen, Min-Chi Chen
1Department of Nuclear Medicine, Chang Gung Memorial Hospital at Lin-kou and Kee-long, Chang Gung University, Taiwan.
Unlabelled:
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 (99m)Tc-TRODAT-1 ([(99m)Tc][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) (99m)Tc-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:
(99m)Tc-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.
Insights
Dopamine transporter (DAT) levels are reduced in Machado-Joseph disease (MJD) patients and even in asymptomatic carriers. (99m)Tc-TRODAT-1 brain SPECT imaging reveals early presynaptic dopamine neuron dysfunction in MJD gene carriers.
Area of Science:
- Neuroscience
- Radiology
- Genetics
Background:
- Machado-Joseph disease (MJD) is characterized by decreased dopamine transporter (DAT) binding.
- Early detection of DAT activity changes in asymptomatic MJD (aMJD) gene carriers is crucial for understanding disease progression.
Purpose of the Study:
- To investigate dopamine transporter (DAT) activity in asymptomatic MJD (aMJD) gene carriers using brain SPECT.
- To compare DAT binding in aMJD gene carriers, MJD patients, and healthy controls.
Main Methods:
- Prospective study involving 5 aMJD gene carriers, 10 MJD patients, and 10 healthy controls.
- Brain SPECT imaging using (99m)Tc-TRODAT-1, a DAT-specific tracer.
- Measurement of tracer uptake in the striatum by fusing SPECT images with MRI-derived striatal atlases.
Main Results:
- Significant reduction in DAT uptake was observed in both aMJD gene carriers (P < 0.001) and MJD patients (P < 0.001) compared to controls.
- The reduction in DAT binding was more severe in MJD patients than in aMJD gene carriers.
- Lower bilateral putamen-to-caudate ratios were found in both aMJD gene carriers and MJD patients (P < 0.001), indicating prominent dopamine neuron affection in the putamen.
Conclusions:
- (99m)Tc-TRODAT-1 brain SPECT can detect early alterations in dopamine neurons within the striatal region.
- Presynaptic dopamine function impairment occurs at an early, previously unrecognized stage in aMJD gene carriers.
- This imaging technique holds potential for early diagnosis and monitoring of MJD.