European multicentre database of healthy controls for [123I]FP-CIT SPECT (ENC-DAT): age-related effects, gender differences and evaluation of different methods of analysis

  • Andrea VarroneEmail author
  • John C. Dickson
  • Livia Tossici-Bolt
  • Terez Sera
  • Susanne Asenbaum
  • Jan Booij
  • Ozlem L. Kapucu
  • Andreas Kluge
  • Gitte M. Knudsen
  • Pierre Malick Koulibaly
  • Flavio Nobili
  • Marco Pagani
  • Osama Sabri
  • Thierry Vander Borght
  • Koen Van Laere
  • Klaus Tatsch
Original Article



Dopamine transporter (DAT) imaging with [123I]FP-CIT (DaTSCAN) is an established diagnostic tool in parkinsonism and dementia. Although qualitative assessment criteria are available, DAT quantification is important for research and for completion of a diagnostic evaluation. One critical aspect of quantification is the availability of normative data, considering possible age and gender effects on DAT availability. The aim of the European Normal Control Database of DaTSCAN (ENC-DAT) study was to generate a large database of [123I]FP-CIT SPECT scans in healthy controls.


SPECT data from 139 healthy controls (74 men, 65 women; age range 20 – 83 years, mean 53 years) acquired in 13 different centres were included. Images were reconstructed using the ordered-subset expectation-maximization algorithm without correction (NOACSC), with attenuation correction (AC), and with both attenuation and scatter correction using the triple-energy window method (ACSC). Region-of-interest analysis was performed using the BRASS software (caudate and putamen), and the Southampton method (striatum). The outcome measure was the specific binding ratio (SBR).


A significant effect of age on SBR was found for all data. Gender had a significant effect on SBR in the caudate and putamen for the NOACSC and AC data, and only in the left caudate for the ACSC data (BRASS method). Significant effects of age and gender on striatal SBR were observed for all data analysed with the Southampton method. Overall, there was a significant age-related decline in SBR of between 4 % and 6.7 % per decade.


This study provides a large database of [123I]FP-CIT SPECT scans in healthy controls across a wide age range and with balanced gender representation. Higher DAT availability was found in women than in men. An average age-related decline in DAT availability of 5.5 % per decade was found for both genders, in agreement with previous reports. The data collected in this study may serve as a reference database for nuclear medicine centres and for clinical trials using [123I]FP-CIT SPECT as the imaging marker.


Dopamine transporter Gender difference Age effects SPECT Scatter correction Database 



The participating centres thank GE Healthcare and the German Parkinson Association for their financial contribution to this study, ABX-CRO for managing the network activities and the Executive Committee of the EANM for establishing the EANM Research Ltd. (EARL) as an administrative framework for this project. The authors also thank the personnel of each Nuclear Medicine Centre responsible for the quality controls and acquisition of the SPECT data.


Prof. Jan Booij is a consultant for GE Healthcare.

Supplementary material

259_2012_2276_MOESM1_ESM.jpg (3 mb)
Supplementary Figure 1 Age distribution for males (A) and females (B) included in each centre (listed in alphabetical order). The gamma-camera system used for the SPECT acquisition is in parenthesis. (JPEG 3033 kb)
259_2012_2276_MOESM2_ESM.jpg (3.1 mb)
ESM 1 (JPEG 3178 kb)


  1. 1.
    Tatsch K. Can SPET imaging of dopamine uptake sites replace PET imaging in Parkinson’s disease? For. Eur J Nucl Med Mol Imaging. 2002;29:711–4.PubMedCrossRefGoogle Scholar
  2. 2.
    Marshall V, Grosset DG. Role of dopamine transporter imaging in the diagnosis of atypical tremor disorders. Mov Disord. 2003;18 Suppl 7:S22–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Benamer TS, Patterson J, Grosset DG, Booij J, de Bruin K, van Royen E, et al. Accurate differentiation of parkinsonism and essential tremor using visual assessment of [123I]-FP-CIT SPECT imaging: the [123I]-FP-CIT study group. Mov Disord. 2000;15:503–10.PubMedCrossRefGoogle Scholar
  4. 4.
    Catafau AM, Tolosa E. Impact of dopamine transporter SPECT using 123I-Ioflupane on diagnosis and management of patients with clinically uncertain Parkinsonian syndromes. Mov Disord. 2004;19:1175–82.PubMedCrossRefGoogle Scholar
  5. 5.
    McKeith I, O’Brien J, Walker Z, Tatsch K, Booij J, Darcourt J, et al. Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study. Lancet Neurol. 2007;6:305–13.PubMedCrossRefGoogle Scholar
  6. 6.
    Darcourt J, Booij J, Tatsch K, Varrone A, Vander Borght T, Kapucu OL, et al. EANM procedure guidelines for brain neurotransmission SPECT using (123)I-labelled dopamine transporter ligands, version 2. Eur J Nucl Med Mol Imaging. 2010;37:443–50.PubMedCrossRefGoogle Scholar
  7. 7.
    Whone AL, Watts RL, Stoessl AJ, Davis M, Reske S, Nahmias C, et al. Slower progression of Parkinson’s disease with ropinirole versus levodopa: the REAL-PET study. Ann Neurol. 2003;54:93–101.PubMedCrossRefGoogle Scholar
  8. 8.
    Fahn S, Oakes D, Shoulson I, Kieburtz K, Rudolph A, Lang A, et al. Levodopa and the progression of Parkinson’s disease. N Engl J Med. 2004;351:2498–508.PubMedCrossRefGoogle Scholar
  9. 9.
    van Dyck CH, Seibyl JP, Malison RT, Laruelle M, Wallace E, Zoghbi SS, et al. Age-related decline in striatal dopamine transporter binding with iodine-123-beta-CITSPECT. J Nucl Med. 1995;36:1175–81.PubMedGoogle Scholar
  10. 10.
    Lavalaye J, Booij J, Reneman L, Habraken JB, van Royen EA. Effect of age and gender on dopamine transporter imaging with [123I]FP-CIT SPET in healthy volunteers. Eur J Nucl Med. 2000;27:867–9.PubMedCrossRefGoogle Scholar
  11. 11.
    de Rijk MC, Tzourio C, Breteler MM, Dartigues JF, Amaducci L, Lopez-Pousa S, et al. Prevalence of parkinsonism and Parkinson’s disease in Europe: the EUROPARKINSON Collaborative Study. European Community concerted action on the epidemiology of Parkinson’s disease. J Neurol Neurosurg Psychiatry. 1997;62:10–5.PubMedCrossRefGoogle Scholar
  12. 12.
    de Rijk MC, Launer LJ, Berger K, Breteler MM, Dartigues JF, Baldereschi M, et al. Prevalence of Parkinson’s disease in Europe: a collaborative study of population-based cohorts. Neurologic diseases in the elderly research group. Neurology. 2000;54:S21–3.PubMedGoogle Scholar
  13. 13.
    Wooten GF, Currie LJ, Bovbjerg VE, Lee JK, Patrie J. Are men at greater risk for Parkinson’s disease than women? J Neurol Neurosurg Psychiatry. 2004;75:637–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Derogatis LR, Lipman RS, Covi L. SCL-90: an outpatient psychiatric rating scale – preliminary report. Psychopharmacol Bull. 1973;9:13–28.PubMedGoogle Scholar
  15. 15.
    Beck AT, Steer RA. Beck depression inventory – manual. San Antonio: The Psychological Association; 1987.Google Scholar
  16. 16.
    de Leeuw FE, de Groot JC, Achten E, Oudkerk M, Ramos LM, Heijboer R, et al. Prevalence of cerebral white matter lesions in elderly people: a population based magnetic resonance imaging study. The Rotterdam scan study. J Neurol Neurosurg Psychiatry. 2001;70:9–14.PubMedCrossRefGoogle Scholar
  17. 17.
    Oldfield RC. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia. 1971;9:97–113.PubMedCrossRefGoogle Scholar
  18. 18.
    Dickson JC, Tossici-Bolt L, Sera T, de Nijs R, Booij J, Bagnara MC, et al. Proposal for the standardisation of multi-centre trials in nuclear medicine imaging: prerequisites for a European 123I-FP-CIT SPECT database. Eur J Nucl Med Mol Imaging. 2012;39:188–97.PubMedCrossRefGoogle Scholar
  19. 19.
    Tossici-Bolt L, Dickson JC, Sera T, de Nijs R, Bagnara MC, Jonsson C, et al. Calibration of gamma camera systems for a multicentre European 123I-FP-CIT SPECT normal database. Eur J Nucl Med Mol Imaging. 2011;38:1529–40.PubMedCrossRefGoogle Scholar
  20. 20.
    Ichihara T, Ogawa K, Motomura N, Kubo A, Hashimoto S. Compton scatter compensation using the triple-energy window method for single- and dual-isotope SPECT. J Nucl Med. 1993;34:2216–21.PubMedGoogle Scholar
  21. 21.
    Hudson HM, Larkin RS. Accelerated image reconstruction using ordered subsets of projection data. IEEE Trans Med Imaging. 1994;13:601–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Dickson JC, Tossici-Bolt L, Sera T, Erlandsson K, Varrone A, Tatsch K, et al. The impact of reconstruction method on the quantification of DaTSCAN images. Eur J Nucl Med Mol Imaging. 2010;37:23–35.PubMedCrossRefGoogle Scholar
  23. 23.
    Ogawa K, Harata Y, Ichihara T, Kubo A, Hashimoto S. A practical method for position-dependent Compton-scatter correction in single photon emission CT. IEEE Trans Med Imaging. 1991;10:408–12.PubMedCrossRefGoogle Scholar
  24. 24.
    Koch W, Suessmair C, Tatsch K, Popperl G. Iterative reconstruction or filtered backprojection for semi-quantitative assessment of dopamine D receptor SPECT studies? Eur J Nucl Med Mol Imaging. 2011;38:1095–103.PubMedCrossRefGoogle Scholar
  25. 25.
    Tossici-Bolt L, Hoffmann SM, Kemp PM, Mehta RL, Fleming JS. Quantification of [123I]FP-CIT SPECT brain images: an accurate technique for measurement of the specific binding ratio. Eur J Nucl Med Mol Imaging. 2006;33:1491–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Gunning-Dixon FM, Head D, McQuain J, Acker JD, Raz N. Differential aging of the human striatum: a prospective MR imaging study. AJNR Am J Neuroradiol. 1998;19:1501–7.PubMedGoogle Scholar
  27. 27.
    Cohen J, Cohen P, West SG, Aiken LS. Applied multiple regression/correlation analysis for the behavioral sciences. Mahwah: Erlbaum; 2003.Google Scholar
  28. 28.
    Staley JK, Krishnan-Sarin S, Zoghbi S, Tamagnan G, Fujita M, Seibyl JP, et al. Sex differences in [123I]beta-CIT SPECT measures of dopamine and serotonin transporter availability in healthy smokers and nonsmokers. Synapse. 2001;41:275–84.PubMedCrossRefGoogle Scholar
  29. 29.
    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.PubMedCrossRefGoogle Scholar
  30. 30.
    Ryding E, Lindstrom M, Bradvik B, Grabowski M, Bosson P, Traskman-Bendz L, et al. A new model for separation between brain dopamine and serotonin transporters in 123I-beta-CIT SPECT measurements: normal values and sex and age dependence. Eur J Nucl Med Mol Imaging. 2004;31:1114–8.PubMedCrossRefGoogle Scholar
  31. 31.
    van Dyck CH, Seibyl JP, Malison RT, Laruelle M, Zoghbi SS, Baldwin RM, et al. Age-related decline in dopamine transporters: analysis of striatal subregions, nonlinear effects, and hemispheric asymmetries. Am J Geriatr Psychiatry. 2002;10:36–43.PubMedGoogle Scholar
  32. 32.
    Sanchez MG, Morissette M, Di Paolo T. Effect of a chronic treatment with 17beta-estradiol on striatal dopamine neurotransmission and the Akt/GSK3 signaling pathway in the brain of ovariectomized monkeys. Psychoneuroendocrinology. 2012;37:280–91.PubMedCrossRefGoogle Scholar
  33. 33.
    Barnden LR, Dickson J, Hutton BF. Detection and validation of the body edge in low count emission tomography images. Comput Methods Programs Biomed. 2006;84:153–61.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Andrea Varrone
    • 1
    Email author
  • John C. Dickson
    • 2
  • Livia Tossici-Bolt
    • 3
  • Terez Sera
    • 4
  • Susanne Asenbaum
    • 5
  • Jan Booij
    • 6
  • Ozlem L. Kapucu
    • 7
  • Andreas Kluge
    • 8
  • Gitte M. Knudsen
    • 9
  • Pierre Malick Koulibaly
    • 10
  • Flavio Nobili
    • 11
  • Marco Pagani
    • 12
    • 13
  • Osama Sabri
    • 14
  • Thierry Vander Borght
    • 15
  • Koen Van Laere
    • 16
  • Klaus Tatsch
    • 17
  1. 1.Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry ResearchKarolinska University Hospital, R5:02StockholmSweden
  2. 2.Institute of Nuclear MedicineUCLH NHS Foundation Trust and University CollegeLondonUK
  3. 3.Department of Medical PhysicsUniversity Hospitals Southampton NHS TrustSouthamptonUK
  4. 4.Department of Nuclear Medicine and Euromedic SzegedUniversity of SzegedSzegedHungary
  5. 5.Department of Nuclear MedicineMedical University of ViennaViennaAustria
  6. 6.Department of Nuclear Medicine, Academic Medical CentreUniversity of AmsterdamAmsterdamNetherlands
  7. 7.Department of Nuclear Medicine, Faculty of MedicineGazi UniversityAnkaraTurkey
  8. 8.ABX-CRODresdenGermany
  9. 9.Neurobiology Research UnitRigshospitalet and University of CopenhagenCopenhagenDenmark
  10. 10.Nuclear Medicine Department, Centre Antoine LacassagneUniversity of Nice-Sophia AntipolisNiceFrance
  11. 11.Clinical Neurophysiology Unit, Department of Neuroscience, Ophthalmology and GeneticsUniversity of GenoaGenoaItaly
  12. 12.Institute of Cognitive Sciences and Technologies, CNRRomeItaly
  13. 13.Department of Nuclear MedicineKarolinska University HospitalStockholmSweden
  14. 14.Department of Nuclear MedicineUniversity of LeipzigLeipzigGermany
  15. 15.Nuclear Medicine Division, Mont-Godinne Medical CenterUniversité Catholique de LouvainYvoirBelgium
  16. 16.Nuclear MedicineUniversity Hospital and K.U. LeuvenLeuvenBelgium
  17. 17.Department of Nuclear MedicineMunicipal Hospital of Karlsruhe IncKarlsruheGermany

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