Differences in [99mTc]TRODAT-1 SPECT binding to dopamine transporters in patients with multiple system atrophy and Parkinson’s disease

  • Randel L. Swanson
  • Andrew B. Newberg
  • Paul D. Acton
  • Andrew Siderowf
  • Nancy Wintering
  • Abass Alavi
  • P. David Mozley
  • Karl Plossl
  • Michelle Udeshi
  • Howard Hurtig
Original Article



Multiple system atrophy (MSA), a disorder causing autonomic dysfunction, parkinsonism, and cerebellar dysfunction, is difficult to differentiate from other movement disorders, particularly early in the course of disease. This study evaluated whether [99mTc]TRODAT-1 binding to the dopamine transporter differentiates MSA from other movement disorders.


Single-photon emission computed tomographic brain scans were acquired in 25 MSA patients, 48 age-matched controls, and 130 PD patients, 3 h after the injection of 740 MBq (20 mCi) of [99mTc]TRODAT-1. Regions of interest (ROIs) were placed manually on subregions of both basal ganglia and distribution volume ratios (DVRs) were calculated. Regional DVRs were compared between study groups in MSA patients. Student’s t tests were used to compare MSA patients with other study groups. Spearman correlations were used to compare DVRs with NP measures.


Based upon various motor scores, MSA and PD patients had comparable motor impairment, and were significantly impaired compared with controls. Mean DVRs in the basal ganglia of MSA patients were significantly less than those of controls, but generally higher (p<0.05) than in PD patients. In particular, the MSA patients had significantly increased DVRs in the posterior putamen (mean 0.49±0.30) compared with PD patients (0.74±0.25).


Movement disorder patients could be differentiated from controls, but MSA and PD patients could not be easily differentiated from each other. As a group, MSA patients had significantly higher mean [99mTc]TRODAT-1 binding, particularly in the posterior putamen, compared with PD patients and significantly lower binding compared with controls. This may reflect different pathophysiological processes of the two neurodegenerative diseases.


Dopamine transporter Parkinson’s disease Multiple system atrophy Single-photon emission computed tomography 


  1. 1.
    Gilman S, Low PA, Quinn N, Albanese A, Ben-Shlomo Y, Fowler CJ, et al. Consensus statement on the diagnosis of multiple system atrophy. J Neurol Sci 1999;163:94–8.CrossRefPubMedGoogle Scholar
  2. 2.
    Wenning GK, Braune S. Multiple system atrophy: pathophysiology and management. CNS Drugs 2001;15:839–52.PubMedGoogle Scholar
  3. 3.
    Tison F, Yekhlef F, Chrysostome V, Balestre E, Quinn NP, Poewe W, Wenning GK. Parkinsonism in multiple system atrophy: natural history, severity (UPDRS-III), and disability assessment compared with Parkinson’s disease. Mov Disord 2002;17:701–92.CrossRefPubMedGoogle Scholar
  4. 4.
    Lang AE, Lozano AM. Parkinson’s disease. First of two parts. N Engl J Med 1998;339:1044–53.CrossRefPubMedGoogle Scholar
  5. 5.
    Lang AE, Lozano AM. Parkinson’s disease. Second of two parts. N Engl J Med 1998;339:1130–43.CrossRefPubMedGoogle Scholar
  6. 6.
    Stern MB, Koller WC. Parkinson’s disease. In: Stern MB, Koller WC, editors. Parkinsonian syndromes. New York: Marcel; 1993. p. 3–29.Google Scholar
  7. 7.
    Jankovic J. Pathophysiology and clinical assessment of motor symptoms in Parkinson’s disease. In: Koller WC, editor. Handbook of Parkinson’s disease. New York: Marcel; 1992. p. 129–57.Google Scholar
  8. 8.
    Rajput AH, Rozdilsky B, Rajput A. Accuracy of clinical diagnosis in parkinsonism—a prospective study. Can J Neurol Sci 1991;18:275–8.PubMedGoogle Scholar
  9. 9.
    Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 1992;55:181–4.Google Scholar
  10. 10.
    Hughes AJ, Daniel SE, Lees AJ. Improved accuracy of clinical diagnosis of Lewy body Parkinson’s disease. Neurology 2001;57:1497–9.PubMedGoogle Scholar
  11. 11.
    Hughes AJ, Daniel SE, Ben-Shlomo Y, Lees AJ. The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service. Brain 2002;125:861–70.CrossRefPubMedGoogle Scholar
  12. 12.
    Hughes AJ, Colosimo C, Kleedorfer B, Daniel SE, Lees AJ. The dopaminergic response in multiple system atrophy. Neurol Neurosurg Psychiatry 1992;55:1009–13.Google Scholar
  13. 13.
    Mozley PD, Schneider JS, Acton PD, Plossl K, Stern MB, Siderowf A, et al. Binding of [99mTc]TRODAT-1 to dopamine transporters in patients with Parkinson’s disease and in healthy volunteers. J Nucl Med 2000;41:584–9.PubMedGoogle Scholar
  14. 14.
    Lu CS, Weng YH, Chen MC, Chen RS, Tzen KY, Wey SP, et al. 99mTc-TRODAT-1 imaging of multiple system atrophy. J Nucl Med 2004;45:49–55.PubMedGoogle Scholar
  15. 15.
    Ishikawa T, Dhawan V, Kazumata K, Chaly T, Mandel F, Neumeyer J, et al. Comparative nigrostriatal dopaminergic imaging with iodine-123-βCIT-FP/SPECT and fluorine-18-FDOPA/PET. J Nucl Med 1996;37:1760–5.PubMedGoogle Scholar
  16. 16.
    Innis RB, Seibyl JP, Scanley BE, Laruelle M, Abi-Dargham A, Wallace E, et al. Single-photon emission computed tomographic imaging demonstrates loss of striatal dopamine transporters in Parkinson’s disease. Proc Natl Acad Sci U S A 1993;90:11965–9.PubMedGoogle Scholar
  17. 17.
    Kung HF, Kim HJ, Kung MP, Meegala SK, Plossl K, Lee HK. Imaging of dopamine transporters in humans with technetium-99m TRODAT-1. Eur J Nucl Med 1996;23:1527–30.PubMedGoogle Scholar
  18. 18.
    Mozley PD, Stubbs JB, Plossl K, Dresel SH, Barraclough ED, Alavi A, et al. Biodistribution and dosimetry of TRODAT-1: a technetium-99m tropane for imaging dopamine transporters. J Nucl Med 1998;39:2069–76.PubMedGoogle Scholar
  19. 19.
    Ward CD, Gibbs WR. Research diagnostic criteria for Parkinson’s disease. In: Streifler MB, Korczyn AD, Melamed E, Youdin MBH, editors. Advances in neurology: anatomy, pathology and therapy. New York: Raven; 1990.Google Scholar
  20. 20.
    Dresel SH, Kung MP, Plossl K, Meegalla SK, Kung HF. Pharmacological effects of dopaminergic drugs on in vivo binding of [99mTc]TRODAT-1 to the central dopamine transporters in rats. Eur J Nucl Med 1998;25:31–9.CrossRefPubMedGoogle Scholar
  21. 21.
    Mozley LH, Gur RC, Mozley PD, Gur RE. Striatal dopamine transporters and cognitive functioning in healthy men and women. Am J Psychiatry 2001;158:1492–9.CrossRefPubMedGoogle Scholar
  22. 22.
    Golden CJ, Hammeke TA, Purisch AD. Luria-Nebraska neuropsychological battery manual. Los Angeles: Western Psychological; 1980.Google Scholar
  23. 23.
    Reitan RM, Wolfson D. The Halstead-Reitan neuropsychological test battery: theory and clinical interpretation. Tuscon: Neuropsychology; 1985.Google Scholar
  24. 24.
    Harley JP, Leuthold CA, Matthews CG, Bergs LE. Wisconsin neuropsychological test battery t-score norms for older Veterans Administration Medical Center patients. Madison: Matthews; 1980.Google Scholar
  25. 25.
    Kim HJ, Karp JS, Mozley PD, Yang SO, Moon DH, Kung HF, et al. Stimulating technetium-99m cerebral perfusion studies with a three-dimensional Hoffmann brain phantom: collimator and filter selection in SPECT neuroimaging. Ann Nucl Med 1996;10:153–60.PubMedGoogle Scholar
  26. 26.
    Chang LT. A method for attenuation correction in radionuclide computed tomography. IEEE Trans Nucl Sci 1978;25:638–43.Google Scholar
  27. 27.
    Mozley PD, Acton PD, Barraclough ED, Plossl K, Gur RC, Alavi A, et al. Effects of age on dopamine transporters in healthy humans. J Nucl Med 1999;40:1812–7.PubMedGoogle Scholar
  28. 28.
    Kim YJ, Ichise M, Ballinger JR, Vines D, Erami SS, Tatschida T, Lang AE. Combination of dopamine transporter and D2 receptor SPECT in the diagnostic evaluation of PD, MSA, and PSP. Mov Disord 2002;17:303–2.CrossRefPubMedGoogle Scholar
  29. 29.
    Berding G, Brucke T, Odin P, Brooks DJ, Kolbe H, Gielow P, et al. [123I]beta-CIT SPECT imaging of dopamine and serotonin transporters in Parkinson’s disease and multiple system atrophy. Nuklearmedizin 2003;42:31–8.PubMedGoogle Scholar
  30. 30.
    Brooks DJ, Ibanez V, Sawle GV, Quinn N, Lees AJ, Mathias CJ, et al. Differing patterns of striatal 18F-dopa uptake in Parkinson’s disease, multiple system atrophy, and progressive supranuclear palsy. Ann Neurol 1990;28:547–55.PubMedGoogle Scholar
  31. 31.
    Antonini A, Leenders KL, Vontobel P, Maguire RP, Missimer J, Psylla M, Gunther I. Complementary PET studies of striatal neuronal function in the differential diagnosis between multiple system atrophy and Parkinson’s disease. Brain 1997;120:2187–95.CrossRefPubMedGoogle Scholar
  32. 32.
    Brooks DJ, Ibanez V, Sawle GV, Playford ED, Quinn N, Mathias CJ, et al. Striatal D2 receptor status in patients with Parkinson’s disease, striatonigral degeneration, and progressive supranuclear palsy. Measured with 11C-raclopride and positron emission tomography. Ann Neurol 1992;31:184–92.PubMedGoogle Scholar
  33. 33.
    Pirker W, Asenbaum S, Wenger S, Kornhuber J, Angelberger P, Deecke L, et al. Iodine-123-epidepride-SPECT: studies in Parkinson’s disease, multiple system atrophy and Huntington’s disease. J Nucl Med 1997;38:1711–7.PubMedGoogle Scholar
  34. 34.
    Ghaemi M, Hilker R, Rudolf J, Sobesky J, Heiss WD. Differentiating multiple system atrophy from Parkinson’s disease: contribution of striatal and midbrain MRI volumetry and multi-tracer PET imaging. J Neurol Neurosurg Psychiatry 2002;73:517–23.CrossRefPubMedGoogle Scholar
  35. 35.
    Schulz JB, Klockgether T, Petersen D, Jauch M, Muller-Schauenburg W, Spieker S, et al. Multiple system atrophy: natural history, MRI morphology, and dopamine receptor imaging with 123IBZM-SPECT. J Neurol Neurosurg Psychiatry 1994;57:1047–56.PubMedGoogle Scholar
  36. 36.
    Wenning GK, Tison F, Ben Shlomo Y, Daniel SE, Quinn NP. Multiple system atrophy: a review of 203 pathologically proven cases. Mov Disord 1997;12:133–47.PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Randel L. Swanson
    • 1
  • Andrew B. Newberg
    • 1
  • Paul D. Acton
    • 1
  • Andrew Siderowf
    • 1
  • Nancy Wintering
    • 1
  • Abass Alavi
    • 1
  • P. David Mozley
    • 1
  • Karl Plossl
    • 1
  • Michelle Udeshi
    • 1
  • Howard Hurtig
    • 1
  1. 1.Division of Nuclear MedicinePhiladelphiaUSA

Personalised recommendations