Nuclear Medicine and Molecular Imaging

, Volume 47, Issue 1, pp 44–51 | Cite as

Differential Diagnosis of Parkinsonism Using Dual-Phase F-18 FP-CIT PET Imaging

  • Soyoung Jin
  • Minyoung Oh
  • Seung Jun Oh
  • Jungsu S. Oh
  • Sang Ju Lee
  • Sun Ju Chung
  • Chong Sik Lee
  • Jae Seung Kim
Original Article



Dopamine transporter (DAT) imaging can demonstrate presynaptic dopaminergic neuronal loss in Parkinson’s disease (PD). However, differentiating atypical parkinsonism (APD) from PD is often difficult. We investigated the usefulness of dual-phase F-18 FP-CIT positron emission tomography (PET) imaging in the differential diagnosis of parkinsonism.


Ninety-eight subjects [five normal, seven drug-induced parkinsonism (DIP), five essential tremor (ET), 24 PD, 20 multiple system atrophy-parkinson type (MSA-P), 13 multiple system atrophy-cerebellar type (MSA-C), 13 progressive supranuclear palsy (PSP), and 11 dementia with Lewy bodies (DLB)] underwent F-18 FP-CIT PET. PET images were acquired at 5 min (early phase) and 3 h (late phase) after F-18 FP-CIT administration (185 MBq). Regional uptake pattern of cerebral and cerebellar hemispheres was assessed on early phase images and striatal DAT binding pattern was assessed on late phase images, using visual, quantitative, and statistical parametric mapping (SPM) analyses.


Striatal DAT binding was normal in normal, ET, DIP, and MSA-C groups, but abnormal in PD, MSA-P, PSP, and DLB groups. No difference was found in regional uptake on early phase images among normal DAT binding groups, except in the MSA-C group. Abnormal DAT binding groups showed different regional uptake pattern on early phase images compared with PD in SPM analysis (FDR < 0.05). When discriminating APD from PD, visual interpretation of the early phase image showed high diagnostic sensitivity and specificity (75.4 % and 100 %, respectively). Regarding the ability to distinguish specific APD, sensitivities were 81 % for MSA-P, 77 % for MSA-C, 23 % for PSP, and 54.5 % for DLB.


Dual-phase F-18 FP-CIT PET imaging is useful in demonstrating striatal DAT loss in neurodegenerative parkinsonism, and also in differentiating APD, particularly MSA, from PD.


Atypical parkinsonism Dual-phase F-18 FP-CIT Positron emission tomography PET 


Conflicts of Interest

The authors declare no conflict of interest


  1. 1.
    Hughes AJ, Daniel SE, Lees AJ. The clinical features of Parkinson’s disease in 100 histologically proven cases. Adv Neurol. 1993;60:595–9.PubMedGoogle Scholar
  2. 2.
    Rajput AH, Offord KP, Beard CM, Kurland LT. Epidemiology of parkinsonism: incidence, classification, and mortality. Ann Neurol. 1984;16:278–82.PubMedCrossRefGoogle Scholar
  3. 3.
    Bower JH, Dickson DW, Taylor L, Maraganore DM, Rocca WA. Clinical correlates of the pathology underlying parkinsonism: a population perspective. Mov Disord. 2002;17:910–6.PubMedCrossRefGoogle Scholar
  4. 4.
    Litvan I, Agid Y, Jankovic J, Goetz C, Brandel JP, Lai EC, et al. Accuracy of clinical criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome). Neurology. 1996;46:922–30.PubMedCrossRefGoogle Scholar
  5. 5.
    Seppi K, Yekhlef F, Diem A, Luginger Wolf E, Mueller J, Tison F, et al. Progression of parkinsonism in multiple system atrophy. J Neurol. 2005;252:91–6.PubMedCrossRefGoogle Scholar
  6. 6.
    Poewe W, Wenning G. The differential diagnosis of Parkinson’s disease. Eur J Neurol. 2002;9 Suppl 3:23–30.PubMedCrossRefGoogle Scholar
  7. 7.
    Litvan I, Bhatia KP, Burn DJ, Goetz CG, Lang AE, McKeith I, et al. Movement Disorders Society Scientific Issues Committee report: SIC Task Force appraisal of clinical diagnostic criteria for Parkinsonian disorders. Mov Disord. 2003;18:467–86.PubMedCrossRefGoogle Scholar
  8. 8.
    Barclay CL, Lang AE. Dystonia in progressive supranuclear palsy. J Neurol Neurosurg Psychiatry. 1997;62:352–6.PubMedCrossRefGoogle Scholar
  9. 9.
    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.PubMedCrossRefGoogle Scholar
  10. 10.
    Bensimon G, Ludolph A, Agid Y, Vidailhet M, Payan C, Leigh PN. Riluzole treatment, survival and diagnostic criteria in Parkinson plus disorders: the NNIPPS study. Brain. 2009;132(Pt 1):156–71.PubMedGoogle Scholar
  11. 11.
    Juh R, Kim J, Moon D, Choe B, Suh T. Different metabolic patterns analysis of Parkinsonism on the 18 F-FDG PET. Eur J Radiol. 2004;51:223–33.PubMedCrossRefGoogle Scholar
  12. 12.
    Van Laere K, Casteels C, De Ceuninck L, Vanbilloen B, Maes A, Mortelmans L, et al. Dual-tracer dopamine transporter and perfusion SPECT in differential diagnosis of parkinsonism using template-based discriminant analysis. J Nucl Med. 2006;47:384–92.PubMedGoogle Scholar
  13. 13.
    Schocke MF, Seppi K, Esterhammer R, Kremser C, Jaschke W, Poewe W, et al. Diffusion-weighted MRI differentiates the Parkinson variant of multiple system atrophy from PD. Neurology. 2002;58:575–80.PubMedCrossRefGoogle Scholar
  14. 14.
    Brooks DJ. Imaging approaches to Parkinson disease. J Nucl Med. 2010;51:596–609.PubMedCrossRefGoogle Scholar
  15. 15.
    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.PubMedCrossRefGoogle Scholar
  16. 16.
    Varrone A, Marek KL, Jennings D, Innis RB, Seibyl JP. [(123)I]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.PubMedCrossRefGoogle Scholar
  17. 17.
    Kazumata K, Dhawan V, Chaly T, Antonini A, Margouleff C, Belakhlef A, et al. Dopamine transporter imaging with fluorine-18-FPCIT and PET. J Nucl Med. 1998;39:1521–30.PubMedGoogle Scholar
  18. 18.
    Kim JS. Practical Approach for the Clinal Use of Dopamine Transporter Imaging. Nucl Med Mol Imaging. 2008;42(6):425–34.Google Scholar
  19. 19.
    Maqsood Y, Ronald B, van Berckel BNM, Ponsen MM, Mark L, Windhorst AD, et al. Quantification of dopamine transporter binding using [18 F]FP-β-CIT and positron emmision tomography. J Cereb Blood Flow & Metabol. 2007;27:1397–406.CrossRefGoogle Scholar
  20. 20.
    Kim JS. Quantitative analysis and reproducibility of dopamine transporter density using [18 F]FPCIT positron emission tomography. Ph.D. Thesis, Seoul National University, February 2006.Google Scholar
  21. 21.
    Sokoloff L. Relationships among local functional activity, energy metabolism, and blood flow in the central nervous system. Fed Proc. 1981;40:2311–6.PubMedGoogle Scholar
  22. 22.
    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 Nerosurg Psychiatry. 1992;55(3):181–4.CrossRefGoogle Scholar
  23. 23.
    Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology. 2008;71:670–6.PubMedCrossRefGoogle Scholar
  24. 24.
    Litvan I, MacIntyre A, Goetz CG, Wenning GK, Jellinger K, Verny M, et al. Accuracy of the clinical diagnoses of Lewy body disease, Parkinson disease, and dementia with Lewy bodies: a clinicopathologic study. Arch Neurol. 1998;55:969–78.PubMedCrossRefGoogle Scholar
  25. 25.
    Lee SJ, Oh SJ, Chi DY, Kang SH, Kil HS, Kim JS, et al. One-step high-radiochemical-yield synthesis of [18 F]FP-CIT using a protic solvent system. Nucl Med Biol. 2007;34:345–51.PubMedCrossRefGoogle Scholar
  26. 26.
    Kwon KY, Choi CG, Kim JS, Lee MC, Chung SJ. Comparison of brain MRI and 18 F-FDG PET in the differential diagnosis of multiple system atrophy from Parkinson’s disease. Mov Disord. 2007;22:2352–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Kasanuki K, Iseki E, Fujishiro H, Yamamoto R, Higashi S, Minegishi M, et al. Neuropathological investigation of the hypometabolic regions on positron emission tomography with [(18)F] fluorodeoxyglucose in patients with dementia with Lewy bodies. J Neurol Sci. 2012;314:111–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Kimura N, Hanaki S, Masuda T, Hanaoka T, Hazama Y, Okazaki T, et al. Brain perfusion differences in Parkinsonian disorders. Mov Disord. 2011;26(14):2530–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Sun FT, Schriber RA, Greenia JM, He J, Gitcho A, Jagust WJ. Automated template-based PET region of interest analyses in the aging brain. NeuroImage. 2007;34:608–17.PubMedCrossRefGoogle Scholar
  30. 30.
    Oh SW, Kim YK, Lee BC, Kim BS, Kim JS, Kim JM, et al. Evaluation of Multiple System Atrophy and Early Parkinson’s Disease Using 123I-FP-CIT SPECT. Nucl Med Mol Imaging. 2009;43:10–8.Google Scholar
  31. 31.
    Kim BS, Jang SJ, Eo JS, Park EK, Kim YK, Kim JM, et al. The Discriminating Nature of Dopamine Transporter Image in Parkinsonism: The Competency of Dopaminergic Transporter Imaging in Differential Diagnosis Of Parkinsonism: 123I-FP-CIT SPECT Study. Nucl Med Mol Imaging. 2007;41:272–9.Google Scholar
  32. 32.
    Morrish PK, Sawle GV, Brooks DJ. Clinical and [18 F] dopa PET findings in early Parkinson’s disease. J Neurol Neurosurg Psychiatry. 1995;59:597–600.PubMedCrossRefGoogle Scholar
  33. 33.
    Marek K, Innis R, van Dyck C, Fussell B, Early M, Eberly S, et al. [123I]beta-CIT SPECT imaging assessment of the rate of Parkinson’s disease progression. Neurology. 2001;57:2089–94.PubMedCrossRefGoogle Scholar
  34. 34.
    Antonini A, Benti R, De Notaris R, Tesei S, Zecchinelli A, Sacilotto G, et al. 123I-Ioflupane/SPECT binding to striatal dopamine transporter (DAT) uptake in patients with Parkinson’s disease, multiple system atrophy, and progressive supranuclear palsy. Neurol Sci. 2003;24:149–50.PubMedCrossRefGoogle Scholar
  35. 35.
    Eidelberg D, Moeller JR, Dhawan V, Spetsieris P, Takikawa S, Ishikawa T, et al. The metabolic topography of parkinsonism. J Cereb Blood Flow Metab. 1994;14:783–801.PubMedCrossRefGoogle Scholar
  36. 36.
    Brooks DJ. Functional imaging in relation to parkinsonian syndromes. J Neurol Sci. 1993;115:1–17.PubMedCrossRefGoogle Scholar
  37. 37.
    Eckert T, Barnes A, Dhawan V, Frucht S, Gordon MF, Feigin AS, et al. FDG PET in the differential diagnosis of parkinsonian disorders. NeuroImage. 2005;26:912–21.PubMedCrossRefGoogle Scholar
  38. 38.
    Bosman T, Van Laere K, Santens P. Anatomically standardised 99mTc-ECD brain perfusion SPET allows accurate differentiation between healthy volunteers, multiple system atrophy and idiopathic Parkinson’s disease. Eur J Nucl Med Mol Imaging. 2003;30:16–24.PubMedCrossRefGoogle Scholar
  39. 39.
    Wong CY, Thie J, Gaskill M, Ponto R, Hill J, Tian HY, et al. A statistical investigation of normal regional intra-subject heterogeneity of brain metabolism and perfusion by F-18 FDG and O-15 H2O PET imaging. BMC Nucl Med. 2006;6:4.PubMedCrossRefGoogle Scholar
  40. 40.
    Meyer PT, Hellwig S, Amtage F, Rottenburger C, Sahm U, Reuland P, et al. Dual-biomarker imaging of regional cerebral amyloid load and neuronal activity in dementia with PET and 11C-labeled Pittsburgh compound B. J Nucl Med. 2011;52:393–400.PubMedCrossRefGoogle Scholar
  41. 41.
    Litvan I, Goetz CG, Jankovic J, Wenning GK, Booth V, Bartko JJ, et al. What is the accuracy of the clinical diagnosis of multiple system atrophy? A clinicopathologic study. Arch Neurol. 1997;54:937–44.PubMedCrossRefGoogle Scholar

Copyright information

© Korean Society of Nuclear Medicine 2012

Authors and Affiliations

  • Soyoung Jin
    • 1
  • Minyoung Oh
    • 1
  • Seung Jun Oh
    • 1
  • Jungsu S. Oh
    • 1
  • Sang Ju Lee
    • 1
  • Sun Ju Chung
    • 2
  • Chong Sik Lee
    • 2
  • Jae Seung Kim
    • 1
  1. 1.Department of Nuclear Medicine, Asan Medical Center, College of MedicineUniversity of UlsanSeoulSouth Korea
  2. 2.Department of Neurology, Asan Medical Center, College of MedicineUniversity of UlsanSeoulSouth Korea

Personalised recommendations