Does combined imaging of the pre- and postsynaptic dopaminergic system increase the diagnostic accuracy in the differential diagnosis of parkinsonism?

  • Walter Koch
  • Christine Hamann
  • Perry E. Radau
  • Klaus Tatsch
Original Article

Abstract

Purpose

We hypothesized that combining pre- and postsynaptic quantitative information about the dopaminergic system would provide a higher diagnostic accuracy in the differential diagnosis of parkinsonism than specific striatal D2 receptor binding alone. Therefore, the aim of the study was to introduce new semi-quantitative parameters and evaluate their ability to discriminate between Parkinson’s disease (IPS) and non-idiopathic parkinsonian syndromes (non-IPS).

Methods

In 100 patients (69 IPS, 31 non-IPS), postsynaptic [123I]IBZM and presynaptic [123I]FP-CIT SPECT scans were evaluated by observer-independent techniques. The diagnostic performances of striatal dopamine transporter (DAT) and D2 receptor binding, their respective asymmetries, and a combination of pre- and postsynaptic asymmetry were evaluated with ROC analyses. A logistic regression model was generated combining factors to calculate the probability for each patient of belonging to either diagnostic group.

Results

D2 receptor binding provided a sensitivity of 87.1% and a specificity of 72.5% with an area under the curve (AUC) of 0.866. The AUCs of other single parameters were lower than that of D2 binding. A gain of diagnostic power (p = 0.026) was reached with a model combining pre- and postsynaptic asymmetries and D2 binding (sensitivity 90.3%, specificity 73.9%, AUC 0.893).

Conclusion

The combination of quantitative parameters of presynaptic DAT and postsynaptic D2 receptor binding demonstrates superior diagnostic power in the differentiation of patients with IPS and non-IPS than the established approach based on D2 binding alone. Striatal D2 receptor binding and the combination of DAT and IBZM binding asymmetries are the factors contributing most in separating these diagnostic groups.

Keywords

Quantitative evaluation [123I]IBZM Automatic data processing Asymmetry 

References

  1. 1.
    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
  2. 2.
    Jankovic J, Rajput AH, McDermott MP, Perl DP. The evolution of diagnosis in early Parkinson disease. Parkinson Study Group. Arch Neurol 2000;57:369–72.CrossRefPubMedGoogle Scholar
  3. 3.
    Bokobza B, Ruberg M, Scatton B, Javoy-Agid F, Agid Y. [3H]spiperone binding, dopamine and HVA concentrations in Parkinson’s disease and supranuclear palsy. Eur J Pharmacol 1984;99:167–75.CrossRefPubMedGoogle Scholar
  4. 4.
    Quinn N. Multiple system atrophy-the nature of the beast. J Neurol Neurosurg Psychiatry 1989;Suppl:78–89Google Scholar
  5. 5.
    Schwarz J, Kraft E, Vogl T, Arnold G, Tatsch K, Oertel WH. Relative quantification of signal on T2-weighted images in the basal ganglia: limited value in differential diagnosis of patients with parkinsonism. Neuroradiology 1999;41:124–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Booij J, Tissingh G, Winogrodzka A, van Royen EA. Imaging of the dopaminergic neurotransmission system using single-photon emission tomography and positron emission tomography in patients with parkinsonism. Eur J Nucl Med 1999;26:171–82.CrossRefPubMedGoogle Scholar
  7. 7.
    Brucke T, Djamshidian S, Bencsits G, Pirker W, Asenbaum S, Podreka I. SPECT and PET imaging of the dopaminergic system in Parkinson’s disease. J Neurol 2000;247 Suppl 4:IV/2–7.CrossRefGoogle Scholar
  8. 8.
    Tatsch K. Imaging of the dopaminergic system in parkinsonism with SPET. Nucl Med Commun 2001;22:819–27.CrossRefPubMedGoogle Scholar
  9. 9.
    Tatsch K, Asenbaum S, Bartenstein P, Catafau A, Halldin C, Pilowsky LS, et al. European Association of Nuclear Medicine procedure guidelines for brain neurotransmission SPET using 123I-labelled dopamine D2 receptor ligands. Eur J Nucl Med Mol Imaging 2002;29:BP23–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Plotkin M, Amthauer H, Klaffke S, Kuhn A, Ludemann L, Arnold G, et al. Combined 123I-FP-CIT and 123I-IBZM SPECT for the diagnosis of parkinsonian syndromes: study on 72 patients. J Neural Transm 2005;112:677–92.CrossRefPubMedGoogle Scholar
  11. 11.
    Kim YJ, Ichise M, Ballinger JR, Vines D, Erami SS, Tatschida T, et al. Combination of dopamine transporter and D2 receptor SPECT in the diagnostic evaluation of PD, MSA, and PSP. Mov Disord 2002;17:303–12.CrossRefPubMedGoogle Scholar
  12. 12.
    Bettin S, Kampfer I, Seese A, Schafer A, Reuter M, Lossner J, et al. Striatal uptake of I-123-beta-CIT and I-123-IBZM in patients with extrapyramidal symptoms. Nuklearmedizin 1997;36:167–72.PubMedGoogle Scholar
  13. 13.
    Knudsen GM, Karlsborg M, Thomsen G, Krabbe K, Regeur L, Nygaard T, et al. Imaging of dopamine transporters and D2 receptors in patients with Parkinson’s disease and multiple system atrophy. Eur J Nucl Med Mol Imaging 2004;31:1631–8.CrossRefPubMedGoogle Scholar
  14. 14.
    Koch W, Radau PE, Hamann C, Tatsch K. Clinical testing of an optimized software solution for an automated, observer-independent evaluation of dopamine transporter SPECT studies. J Nucl Med 2005;46:1109–18.PubMedGoogle Scholar
  15. 15.
    Popperl G, Radau P, Linke R, Hahn K, Tatsch K. Diagnostic performance of a 3-D automated quantification method of dopamine D2 receptor SPECT studies in the differential diagnosis of parkinsonism. Nucl Med Commun 2005;26:39–43.CrossRefPubMedGoogle Scholar
  16. 16.
    Buchert R, Berding G, Wilke F, Martin B, von Borczyskowski D, Mester J, et al. IBZM tool: a fully automated expert system for the evaluation of IBZM SPECT studies. Eur J Nucl Med Mol Imaging 2006;33:1073–83.CrossRefPubMedGoogle Scholar
  17. 17.
    Tatsch K, Asenbaum S, Bartenstein P, Catafau A, Halldin C, Pilowsky LS, et al. European Association of Nuclear Medicine procedure guidelines for brain neurotransmission SPET using 123I-labelled dopamine D2 transporter ligands. Eur J Nucl Med Mol Imaging 2002;29:BP30–5.CrossRefPubMedGoogle Scholar
  18. 18.
    Radau PE, Linke R, Slomka PJ, Tatsch K. Optimization of automated quantification of 123I-IBZM uptake in the striatum applied to parkinsonism. J Nucl Med 2000;41:220–7.PubMedGoogle Scholar
  19. 19.
    Larisch R, Klimke A. Clinical impact of cerebral dopamine-D2 receptor scintigraphy. Nuklearmedizin 1998;37:245–50.PubMedGoogle Scholar
  20. 20.
    Schwarz J, Tatsch K, Arnold G, Ott M, Trenkwalder C, Kirsch CM, et al. 123I-iodobenzamide-SPECT in 83 patients with de novo parkinsonism. Neurology 1993;43:S17–20.PubMedGoogle Scholar
  21. 21.
    Schelosky L, Hierholzer J, Wissel J, Cordes M, Poewe W. Correlation of clinical response in apomorphine test with D2-receptor status as demonstrated by 123I IBZM-SPECT. Mov Disord 1993;8:453–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Schneider JA, Watts RL, Gearing M, Brewer RP, Mirra SS. Corticobasal degeneration: neuropathologic and clinical heterogeneity. Neurology 1997;48:959–69.PubMedGoogle Scholar
  23. 23.
    Tissingh G, Booij J, Bergmans P, Winogrodzka A, Janssen AG, van Royen EA, et al. Iodine-123-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane SPECT in healthy controls and early-stage, drug-naive Parkinson’s disease. J Nucl Med 1998;39:1143–8.PubMedGoogle Scholar
  24. 24.
    Rinne UK, Laihinen A, Rinne JO, Nagren K, Bergman J, Ruotsalainen U. Positron emission tomography demonstrates dopamine D2 receptor supersensitivity in the striatum of patients with early Parkinson’s disease. Mov Disord 1990;5:55–9.CrossRefPubMedGoogle Scholar
  25. 25.
    Antonini A, Schwarz J, Oertel WH, Pogarell O, Leenders KL. Long-term changes of striatal dopamine D2 receptors in patients with Parkinson’s disease: a study with positron emission tomography and [11C]raclopride. Mov Disord 1997;12:33–8.CrossRefPubMedGoogle Scholar
  26. 26.
    Ichise M, Kim YJ, Ballinger JR, Vines D, Erami SS, Tanaka F, et al. SPECT imaging of pre- and postsynaptic dopaminergic alterations in L-dopa-untreated PD. Neurology 1999;52:1206–14.PubMedGoogle Scholar
  27. 27.
    Gonzalez AM, Berciano J, Figols J, Pazos A, Pascual J. Loss of dopamine uptake sites and dopamine D2 receptors in striatonigral degeneration. Brain Res 2000;852:228–32.CrossRefPubMedGoogle Scholar
  28. 28.
    Pascual J, Berciano J, Grijalba B, del Olmo E, Gonzalez AM, Figols J, et al. Dopamine D1 and D2 receptors in progressive supranuclear palsy: an autoradiographic study. Ann Neurol 1992;32:703–7.CrossRefPubMedGoogle Scholar
  29. 29.
    Varrone A, Marek KL, Jennings D, Innis RB, Seibyl JP. [123I]beta-CIT SPECT imaging demonstrates reduced density of striatal dopamine transporters in Parkinson’s disease and multiple system atrophy. Mov Disord 2001;16:1023–32.CrossRefPubMedGoogle Scholar
  30. 30.
    Brucke T, Asenbaum S, Pirker W, Djamshidian S, Wenger S, Wober C, et al. Measurement of the dopaminergic degeneration in Parkinson’s disease with [123I]beta-CIT and SPECT. Correlation with clinical findings and comparison with multiple system atrophy and progressive supranuclear palsy. J Neural Transm Suppl 1997;50:9–24.PubMedGoogle Scholar
  31. 31.
    Seibyl JP, Marek KL, Quinlan D, Sheff K, Zoghbi S, Zea-Ponce Y, et al. Decreased single-photon emission computed tomographic [123I]beta-CIT striatal uptake correlates with symptom severity in Parkinson’s disease. Ann Neurol 1995;38:589–98.CrossRefPubMedGoogle Scholar
  32. 32.
    Tissingh G, Bergmans P, Booij J, Winogrodzka A, van Royen EA, Stoof JC, et al. Drug-naive patients with Parkinson’s disease in Hoehn and Yahr stages I and II show a bilateral decrease in striatal dopamine transporters as revealed by [123I]beta-CIT SPECT. J Neurol 1998;245:14–20.CrossRefPubMedGoogle Scholar
  33. 33.
    Rinne JO, Ruottinen H, Bergman J, Haaparanta M, Sonninen P, Solin O. Usefulness of a dopamine transporter PET ligand [18F]beta-CFT in assessing disability in Parkinson’s disease. J Neurol Neurosurg Psychiatry 1999;67:737–41.PubMedCrossRefGoogle Scholar
  34. 34.
    Kim SE, Lee WY, Choe YS, Kim JH. SPECT measurement of iodine-123-beta-CIT binding to dopamine and serotonin transporters in Parkinson’s disease: correlation with symptom severity. Neurol Res 1999;21:255–61.PubMedGoogle Scholar
  35. 35.
    Pirker W. Correlation of dopamine transporter imaging with parkinsonian motor handicap: how close is it? Mov Disord 2003;18 Suppl 7:S43–51.CrossRefPubMedGoogle Scholar
  36. 36.
    Asenbaum S, Brucke T, Pirker W, Podreka I, Angelberger P, Wenger S, et al. Imaging of dopamine transporters with iodine-123-beta-CIT and SPECT in Parkinson’s disease. J Nucl Med 1997;38:1–6.PubMedGoogle Scholar
  37. 37.
    Pirker W, Asenbaum S, Bencsits G, Prayer D, Gerschlager W, Deecke L, et al. [123I]beta-CIT SPECT in multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration. Mov Disord 2000;15:1158–67.CrossRefPubMedGoogle Scholar
  38. 38.
    McNeill TH, Brown SA, Rafols JA, Shoulson I. Atrophy of medium spiny I striatal dendrites in advanced Parkinson’s disease. Brain Res 1988;455:148–52.CrossRefPubMedGoogle Scholar
  39. 39.
    Brooks DJ. PET studies on the early and differential diagnosis of Parkinson’s disease. Neurology 1993;43:S6–16.PubMedGoogle Scholar
  40. 40.
    Rice JE, Thompson PD. 5: Movement disorders I: parkinsonism and the akinetic-rigid syndromes. Med J Aust 2001;174:357–63.PubMedGoogle Scholar
  41. 41.
    Rinne JO, Hietala J, Ruotsalainen U, Sako E, Laihinen A, Nagren K, et al. Decrease in human striatal dopamine D2 receptor density with age: a PET study with [11C]raclopride. J Cereb Blood Flow Metab 1993;13:310–4.PubMedGoogle Scholar
  42. 42.
    Wong DF, Young D, Wilson PD, Meltzer CC, Gjedde A. Quantification of neuroreceptors in the living human brain: III. D2-like dopamine receptors: theory, validation, and changes during normal aging. J Cereb Blood Flow Metab 1997;17:316–30.CrossRefPubMedGoogle Scholar
  43. 43.
    Volkow ND, Wang GJ, Fowler JS, Logan J, Gatley SJ, MacGregor RR, et al. Measuring age-related changes in dopamine D2 receptors with 11C-raclopride and 18F-N-methylspiroperidol. Psychiatry Res 1996;67:11–6.CrossRefPubMedGoogle Scholar
  44. 44.
    Ichise M, Ballinger JR, Tanaka F, Moscovitch M, St George-Hyslop PH, Raphael D, et al. Age-related changes in D2 receptor binding with iodine-123-iodobenzofuran SPECT. J Nucl Med 1998;39:1511–8.PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Walter Koch
    • 1
  • Christine Hamann
    • 2
  • Perry E. Radau
    • 3
  • Klaus Tatsch
    • 1
  1. 1.Department of Nuclear MedicineUniversity of MunichMunichGermany
  2. 2.Department of NeurologyUniversity of MunichMunichGermany
  3. 3.Department of Medical BiophysicsSunnybrook and Women’s College Health SciencesTorontoCanada

Personalised recommendations