Dopamine transporter concentration is reduced in asymptomatic Machado-Joseph disease gene carriers

Tzu Chen Yen, Kai Yuan Tzen, Min Chi Chen, Yah Huei Wu Chou, Rou Shayn Chen, Chi Jen Chen, Shiaw Pyng Wey, Gann Ting, Chin Song Lu

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)153-159
Number of pages7
JournalJournal of Nuclear Medicine
Volume43
Issue number2
Publication statusPublished - 2002
Externally publishedYes

Fingerprint

Machado-Joseph Disease
Dopamine Plasma Membrane Transport Proteins
Single-Photon Emission-Computed Tomography
Corpus Striatum
Genes
Putamen
Dopamine
Brain
Ethane
Atlases
Dopaminergic Neurons
Intravenous Injections
Healthy Volunteers
Prospective Studies

Keywords

  • Tc-TRODAT-1 brain SPECT
  • Asymptomatic Machado-Joseph gene carrier
  • Dopamine transporter
  • Machado-Joseph disease

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

Cite this

Yen, T. C., Tzen, K. Y., Chen, M. C., Chou, Y. H. W., Chen, R. S., Chen, C. J., ... Lu, C. S. (2002). Dopamine transporter concentration is reduced in asymptomatic Machado-Joseph disease gene carriers. Journal of Nuclear Medicine, 43(2), 153-159.

Dopamine transporter concentration is reduced in asymptomatic Machado-Joseph disease gene carriers. / Yen, Tzu Chen; Tzen, Kai Yuan; Chen, Min Chi; Chou, Yah Huei Wu; Chen, Rou Shayn; Chen, Chi Jen; Wey, Shiaw Pyng; Ting, Gann; Lu, Chin Song.

In: Journal of Nuclear Medicine, Vol. 43, No. 2, 2002, p. 153-159.

Research output: Contribution to journalArticle

Yen, TC, Tzen, KY, Chen, MC, Chou, YHW, Chen, RS, Chen, CJ, Wey, SP, Ting, G & Lu, CS 2002, 'Dopamine transporter concentration is reduced in asymptomatic Machado-Joseph disease gene carriers', Journal of Nuclear Medicine, vol. 43, no. 2, pp. 153-159.
Yen, Tzu Chen ; Tzen, Kai Yuan ; Chen, Min Chi ; Chou, Yah Huei Wu ; Chen, Rou Shayn ; Chen, Chi Jen ; Wey, Shiaw Pyng ; Ting, Gann ; Lu, Chin Song. / Dopamine transporter concentration is reduced in asymptomatic Machado-Joseph disease gene carriers. In: Journal of Nuclear Medicine. 2002 ; Vol. 43, No. 2. pp. 153-159.
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abstract = "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.",
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AU - Tzen, Kai Yuan

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AU - Chou, Yah Huei Wu

AU - Chen, Rou Shayn

AU - Chen, Chi Jen

AU - Wey, Shiaw Pyng

AU - Ting, Gann

AU - Lu, Chin Song

PY - 2002

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N2 - 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.

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.

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