Measurement of the dopaminergic degeneration in Parkinson’s disease with [123I]β-CIT and SPECT

Correlation with clinical findings and comparison with multiple system atrophy and progessive supranuclear palsy
  • T. Brücke
  • S. Asenbaum
  • W. Pirker
  • S. Djamshidian
  • S. Wenger
  • Ch. Wöber
  • Ch. Müller
  • I. Podreka
Part of the Journal of Neural Transmission. Supplementa book series (NEURAL SUPPL, volume 50)


The cocaine derivative [123I]β-CIT binds with high affinity to dopamine uptake sites in the striatum and can be used to visualize dopaminergic nerve terminals in vivo in the human brain with SPECT. It has been validated that the calculation of a simple ratio of specific/nondisplaceable binding during a period of binding-equilibrium in the striatum about 20 hrs after bolus injection of the tracer gives a strong and reliable index of the binding potential of dopamine uptake sites. Previous studies have shown that the dopaminergic deficit in patients with Parkinson’s disease (PD) can clearly be visualized and quantified using this method. Our own results in a group of 113 patients with PD demonstrate a 45% loss of striatal [123I]β-CIT binding in comparison to age corrected control values. Highly significant correlations of SPECT findings with clinical data obtained from the UPDRS rating scale such as akinesia, rigidity, axial symptoms and activities of daily living are demonstrated, while no correlation is found with tremor. The signal loss in a region comprising the whole striatum ranges from 35% in Hoehn/Yahr stage I to over 72% in stage V and is highly significantly correlated to the different stages of disease severity. A comparison of [123I]β-CIT binding in the striatum contralaterally and ipsilaterally to the affected body side in 29 patients with hemiparkinson shows a loss of striatal binding of 41% contralaterally and 30% ipsilaterally. Results from subregional analyses in caudate and putamen show relative sparing of the caudate nucleus in PD. Data in 9 patients with multiple system atrophy (MSA) and 4 patients with progressive supranuclear palsy (PSP) are similar to the findings in PD although the differences between caudate and putamen are somewhat less marked.

These data demonstrate that the dopaminergic nerve cell loss in PD and other disorders with a dopaminergic lesion can be quantified with [123I]β-CIT and SPECT and that hopefully a preclinical or very early diagnosis is made possible. Such studies might also open the way for a better evaluation of neuroprotective strategies in PD. It does not seem to be possible however to differentiate PD and MSA or PSP with this method in individual cases.


Multiple System Atrophy Progressive Supranuclear Palsy Dopamine Transporter Progressive Supranuclear Palsy Progressive Supranuclear Palsy Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Aquilonius SM, Bergström K, Eckernäs SA, Hartvig P, Leenders KL, Lundquist H, Antoni G, Gee A, Rimland A, Uhlin J (1987) In vivo evaluation of striatal dopamine reuptake sites using 11C-nomifensine and positron emission tomography. Acta Neurol Scand 76: 283–287PubMedCrossRefGoogle Scholar
  2. Asenbaum S, Brücke T, Pirker W, Podreka I, Angelberger P, Wenger S, Wöber C, Müller C, Deecke L (1997a) Imaging of dopamine transporters with [123I]β-CIT and SPECT in Parkinson’s disease. J Nucl Med (in press)Google Scholar
  3. Asenbaum S, Brücke T, Pirker W, Wenger S, Podreka I, Deecke L (1997b) The application of [123I]β-CIT and SPECT in the diagnosis of movement disorders. Proceedings of the meeting on Neurospect, AntwerpGoogle Scholar
  4. Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F (1973) Brain dopamine and the syndromes of Parkinson and Huntington. J Neurol Sci 20: 415–455PubMedCrossRefGoogle Scholar
  5. Boja JW, Patel A, Carroll FI, Rahman MA, Philip A, Lewin AH, Kopajtic TA, Kuhar MJ (1991) [125I]RTI-55: a potent ligand for dopamine transporters. Eur J Pharmacol 194: 133–134PubMedCrossRefGoogle Scholar
  6. Boja J, Mitchell WM, Patel A, Kopajtic TA, Carroll FI, Lewin AH, Abraham P, Kuhar MJ (1992) High affinity binding of [125I]RTI-55 to dopamine and serotonin transporters in rat brain. Synapse 12: 27–36PubMedCrossRefGoogle Scholar
  7. Brooks DJ, Ibanez V, Sawle GV, Quinn N, Lees AJ, Mathias CJ, Bannister R, Marsden CD, Frackowiak RSJ (1990) Differing patterns of striatal 18F-Dopa uptake in Parkinson’s disease, multiple system atrophy, and progressive supranuclear palsy. Ann Neurol 28: 547–555PubMedCrossRefGoogle Scholar
  8. Brücke T, Kornhuber J, Angelberger P, Asenbaum S, Frassine H, Podreka I (1993) SPECT imaging of dopamine and serotonin transporters with [123I]β-CIT.Binding kinetics in the human brain. J Neural Transm [GenSect] 94: 137–146CrossRefGoogle Scholar
  9. Brücke T, Asenbaum S, Pozzera A, Hornykiewicz S, Harasko-van der Meer C, Wenger S, Koch G, Pirker W, Wöber C, Müller C (1994) Dopaminergic nerve cell loss in Parkinson’s disease quantified with [123I]β-CIT and SPECT correlates with clinical findings. Mov Disord 9 (S1): 120CrossRefGoogle Scholar
  10. Brücke T, Asenbaum S, Pirker W, Pozzera A, Wenger S, Wöber C, Müller C, Angelberger P, Podreka I (1995) Quantification of the dopaminergic nerve cell loss in Parkinson’s disease with [123I]β-CIT and SPECT. J Cereb Blood Flow Metab 15 [Suppl 1]: 37Google Scholar
  11. Carson RE, Channing MA, Blasberg RG, Dunn BB, Cohen RM, Rice KC, Herscovitch P (1993) Comparison of bolus and infusion methods for receptor quantitation: application to [18F]Cyclofoxy and positron emission tomography. J Cereb Blood Flow Metab 13: 24–42PubMedCrossRefGoogle Scholar
  12. De Keyser JD, Ebinger G, Vauquelin G (1990) Age-related changes in the human nigrostriatal dopaminergic system. Ann Neurol 27: 157–161PubMedCrossRefGoogle Scholar
  13. Eidelberg D, Moeller JR, Dhawan V, Sidits JJ, Ginos JZ, Strother SC, Cedarbaum J, Greene P, Fahn S, Rottenberg DA (1990) The metabolic anatomy of Parkinson’s disease: complementary [18F] fluorodesoxyglucose and [18F] fluorodopa positron emission tomographic studies. Mov Dis 5: 203–213CrossRefGoogle Scholar
  14. Fahn S, Elton R, Members of the Unified Parkinson’s Disease Rating Scale development committee (1987) Unified Parkinson’s disease rating scale. In: Fahn S, Marsden CD, Calne DB, Goldstein M (eds) Recent developments in Parkinson’s disease. Macmillan Healthcare Information, Florham Park, New York, 2: 153–164Google Scholar
  15. Farde L, Halldin C, Müller L, Suhara T, Karlsson P, Hall H (1994) PET study of [HC]beta-CIT binding to monoamine transporters in the monkey and human brain. Synapse 16: 93–103PubMedCrossRefGoogle Scholar
  16. Frost JJ, Rosier AJ, Reich SG (1993) Positron emission tomography imaging of the dopamine transporter with 11C-WIN 35428 reveals marked declines in mild Parkinson’s disease. Ann Neurol 34: 423–431PubMedCrossRefGoogle Scholar
  17. German DC, Manaye K, Smith WK, Woodward DJ, Saper CB (1989) Midbrain dopaminergic cell loss in Parkinson’s disease: computer visualization. Ann Neurol 26: 507–514PubMedCrossRefGoogle Scholar
  18. Goto S, Hirano A, Matsumoto S (1989) Subdivisional involvement of nigrostriatal loop in idiopathic Parkinson’s disease and striatonigral degeneration. Ann Neurol 26: 766–770PubMedCrossRefGoogle Scholar
  19. Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progression and mortality. Neurol 6: 253–259Google Scholar
  20. Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55 (3): 181–184PubMedCrossRefGoogle Scholar
  21. Innis R, Baldwin R, Sybirska E, Zea Y, Lamelle M, Al-Tikriti M, Charney D, Zoghbi S, Smith E, Wisniewski G (1991) Single photon emission computed tomography imaging of monoamine reuptake sites in primate brain with [123I]CIT. Eur J Pharmacol 299: 369–370CrossRefGoogle Scholar
  22. Innis RB, Seibyl JP, Scanley BE, Lamelle M, Abi-Dargham A, Wallace E, Baldwin R, Zea-Ponce Y, Zoghbi S, Wang S (1993) Single photon emission computed tomographic imaging demonstrates loss of striatal dopamine transporters in Parkinson disease. Proc Natl Acad Sci USA 90: 11965–11969PubMedCrossRefGoogle Scholar
  23. Janowsy A, Vocci F, Berger P, Angel I, Zelnik N, Kleinman J, Skolnick P (1987) [3H]GBR-12935 binding to the dopamine transporter is decreased in the caudate nucleus in Parkinson’s disease. J Neurochem 49: 617–621CrossRefGoogle Scholar
  24. Jellinger K, Riederer P, Tomanaga M (1980) Progressive supranuclear palsy: clinicopathological and biochemical studies. J Neural Transm [Suppl] 16: 111–128Google Scholar
  25. Kaufmann MJ, Madras BK (1991) Severe depletion of cocaine recognition sites associated with the dopamine transporter in Parkinson’s diseased striatum. Synapse 49: 43–49CrossRefGoogle Scholar
  26. Kilbourn MR, Sherman PS, Pisani T (1992) Repeated reserpine administration reduces in vivo [18F]GBR 13119 binding to the dopamine uptake site. Eur J Pharmacol 216:109–112PubMedCrossRefGoogle Scholar
  27. Kish SJ, Chang LJ, Mirchandani L (1985) Progressive supranuclear palsy: relationship between extrapyramidal disturbances, dementia, and brain neurotransmitter markers. Ann Neurol 18: 530–536PubMedCrossRefGoogle Scholar
  28. Kish SJ, Shannar K, Hornykiewicz O (1988) Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson’s disease. Pathophysiological and clinical implications. N Engl J Med 318: 876–880PubMedCrossRefGoogle Scholar
  29. Kuikka JT, Bergström KA, Vanninen E, Laulumaa V, Hartikainen P, Länsimies E (1993) Initial experience with single photon emission tomography using iodine-123-labelled 2β-carbomethoxy-3β-(4-iodophenyl)tropane in human brain. Eur J Nucl Med 20:783–786PubMedCrossRefGoogle Scholar
  30. Lamelle M, Baldwin RM, Malison RT, Zea-Ponce Y, Zoghbi SS, Al-Tikriti MS, Sybirska EH, Zimmermann RC, Wisniewski G, Neumeyer JL (1993) SPECT Imaging of dopamine and serotonin transporters with [123I]β-CIT: pharmacological characterization of brain uptake in nonhuman primates. Synapse 13: 295–309CrossRefGoogle Scholar
  31. Lamelle M, Giddings S, Zea-Ponce Y, Charney DS, Neumeyer JL, Baldwin RM, Innis RB (1994a) Methyl 3β-(4-[125I]Iodophenyl) Tropane-2β-Carboxylate in vitro binding to dopamine and serotonin transporters under “physiological” conditions. J Neurochem 62: 978–986Google Scholar
  32. Lamelle M, Wallace E, Seibyl JP, Baldwin RM, Zea-Ponce Y, Zoghbi SS, Neumeyer JL, Charney DS, Hoffer PB, Innis RB (1994b) Graphical, kinetic and equilibrium analyses of in vivo [123I]β-CIT binding to dopamine transporters in healthy human subjects. J Cereb Blood Flow Metab 14: 982–994CrossRefGoogle Scholar
  33. Leenders KL, Salmon EP, Tyrrell P, Perani D, Brooks DJ, Sager H, Jones T, Marsden D, Frackowiak RSJ (1990) The nigrostriatal dopaminergic system assessed in vivo by positron emission tomography in healthy volunteer subjects and patients with Parkinson’s disease. Arch Neurol 47: 1290–1298PubMedCrossRefGoogle Scholar
  34. Madras BK, Spealman RD, Fahey MA, Neumeyer JL, Saha JK, Milius RA (1989) Cocaine receptors labeled by 2β-carbomethoxy-3β-(4-fluorophenyl)tropane. Mol Pharmacol 36: 518–524PubMedGoogle Scholar
  35. Malison RT, Wallace EA, Best S, Gandelman M, Zoghbi SS, Zea-Ponce Y, Baldwin RM, Charney DS, Hoffer PB, Kosten TR (1994) SPECT imaging of dopamine transporters in cocaine dependent and healthy control subjects with 123I-β-CIT. Soc Neurosci Abstr 20 (2): 1625Google Scholar
  36. Malison RT, Vessotskie J, Kung MP, McElgin W, Romaniello G, Kim HJ, Goodman MM, Kung HF (1996) SPECT imaging of striatal dopamine transporters in non-human primates with [123I]IPT. J Nucl Med (in press)Google Scholar
  37. Marek KL, Seibyl JP, Sandridge B, Fussell B, Smith EO, Baldwin RM, Zoghbi S, Hoffer PB, Innis RB (1994) SPECT imaging demonstrates striatal dopamine transporter loss in hemiparkinsonism. Soc Neurosci Abstr 20: 1780Google Scholar
  38. Marek KL, Seibyl JP, Zoghbi S, Zea-Ponce Y, Baldwin RM, Fussell B, Carney DS, van Dyck C, Hoffer PB, Innis RB (1996) [123I]β-CIT-SPECT imaging demonstrates bilateral loss of dopamine transporters in hemi-Parkinson’s disease. Neurology 46: 231–237PubMedCrossRefGoogle Scholar
  39. Neumeyer JL, Wang S, Milius RA, Baldwin RM, Zea-Ponce Y, Hoffer PB, Sybirska E, Al-Tikriti MS, Lamelle M, Innis RB (1991) [123I]2β-carbomethoxy-3β-(4-iodo-phenyl)tropane (β-CIT): high affinity SPECT radiotracer of monoamine re-uptake sites in brain. J Med Chem 34: 3144–3146PubMedCrossRefGoogle Scholar
  40. Niznik HB, Fogel EF, Fassos FF, Seeman P (1991) The dopamine transporter is absent in parkinsonian putamen and reduced in the caudate nucleus. J Neurochem 56:192–198PubMedCrossRefGoogle Scholar
  41. Otsuka M, Ichiya Y, Hosokawa S, Kuwabara Y, Tahara T, Fukumura T, Kato M, Masuda K, Goto I (1991) Striatal blood flow, glucose metabolism and 18F-Dopa uptake: difference in Parkinson’s disease and atypical parkinsonism. J Neurol Neurosurg Psychiatry 54: 898–904PubMedCrossRefGoogle Scholar
  42. Parkinson J (1817) An essay on the shaking palsy. Sherwood, Neely and Jones, LondonGoogle Scholar
  43. Pifl C, Uhl GR (1996) Dopamine Transporter: State of the art in parkinsonism. Mov Dis 11 (S1): 22Google Scholar
  44. Pimoule C, Schoemaker H, Javoy-Agid F, Scatton B, Agid Y, Langer JZ (1983) Decrease in [3H]cocaine binding to the dopamine transporter in Parkinson’s disease. Eur J Pharmacol 95: 145–146PubMedCrossRefGoogle Scholar
  45. Pirker W, Asenbaum S, Kasper S, Walter H, Angelberger P, Koch G, Pozzera A, Deecke L, Podreka I, Brücke T (1995) β-CIT SPECT demonstrates blockade of 5HT-uptake sites by Citalopram in the human brain in vivo. J Neural Transm [Gen Sect] 100: 247–256CrossRefGoogle Scholar
  46. Quinn N (1994) Multiple system atrophy. In: Marsden CD, Fahn S (eds) Movement disorders 3. Butterworths-Heinemann, London, pp 262–281Google Scholar
  47. Rinne JO, Rummukainen J, Paljärvi L, Rinne UK (1989) Dementia in Parkinson’s disease is related to neuronal loss in the medial substantia nigra. Ann Neurol 26: 47–50PubMedCrossRefGoogle Scholar
  48. Rinne JO, Kuikka JT, Bergström KA, Rinne UK (1995) Striatal dopamine transporter in different disability stages of Parkinson’s disease studied with [123I] β-CIT SPECT. Parkinsonism and Related Disorders 1 (1): 47–51PubMedCrossRefGoogle Scholar
  49. Ruberg M, Javoy-Agid F, Hirsch E, Scatton B, Lheureux R, Hauw JJ, Duyckaerts C, Gray F, Morel-Maroger A, Rascol A (1985) Dopaminergic and cholinergic lesions in progressive supranuclear palsy. Ann Neurol 18: 523–529PubMedCrossRefGoogle Scholar
  50. Scheffel U, Dannals RF, Cline EJ, Ricaurte GA, Carrol FI, Abraham P, Lewin AH, Kuhar MJ (1992) [123/125I]RTI-55, an in vivo label for the serotonin transporter. Synapse 11: 134–139PubMedCrossRefGoogle Scholar
  51. Seibyl JP, Marek KL, Quinlan D, Sheff K, Zoghbi S, Zea-Ponce Y, Baldwin RM, Fussell B, Smith EO, Charney DS (1995) Decreased single photon emission computed tomographic [123I] β-CIT striatal uptake correlates with symptom severity in Parkinson’s disease. Ann Neurol 38: 589–598PubMedCrossRefGoogle Scholar
  52. Seibyl JP, Lamelle M, van Dyck CH, Wallace E, Baldwin RM, Zoghbi S, Zea-Ponce Y, Neumeyer JL, Charney DS, Hoffer PB (1996a) Reproducibility of iodine-123-β-CIT SPECT brain measurement of dopamine transporters. J Nucl Med 37: 222–228PubMedGoogle Scholar
  53. Seibyl J, Marek K, Sheff K, Neumeyer J, Innis R (1996b) Comparison of [123I]FP-CIT and [123I]β-CIT for SPECT imaging of dopamine transporters in Parkinson’s disease. J Nucl Med 37: 133PGoogle Scholar
  54. Shaya EK, Scheffel U, Dannals RF, Ricaurte GA, Carrol FI, Wagner HN, Kuhar MJ, Wong DF (1992) In vivo imaging of dopamine uptake sites in primate brain using single photon emission tomography (SPECT) and iodine-123 labeled RTI-55. Synapse 10: 169–172PubMedCrossRefGoogle Scholar
  55. Staley JK, Basile M, Flynn DD, Mash DC (1994) Visualizing dopamine and serotonin transporters in the human brain with the potent cocaine analogue [125]RTI-55: In vitro binding and autoradiographic characterization. J Neurochem 62: 549–556PubMedCrossRefGoogle Scholar
  56. Tedroff J, Aquilonius SM, Hartvig P, Lundqvist H, Gee AG, Uhlin J, Långström B (1988) Monoamine reuptake sites in the human brain evaluated in vivo by means of 11C-nomifensine and positron emission tomography: the effects of age and Parkinson’s disease. Acta Neurol Scand 77: 192–201PubMedCrossRefGoogle Scholar
  57. van Dyck CH, Seibyl JP, Malison RT, Lamelle M, Wallace E, Zoghbi SS, Zea-Ponce Y, Baldwin RM, Charney DS, Hoffer PB (1995) Age-related decline in striatal transporter binding with iodine-123-β-CIT SPECT J Nucl Med 36: 1175–1181PubMedGoogle Scholar
  58. Volkow ND, Fowler JS, Wang GJ (1994) Decreased dopamine transporters with age in healthy human subjects. Ann Neurol 36: 237–239PubMedCrossRefGoogle Scholar
  59. Wilson JM, Nobrega JN, Carroll ME, Niznik HB, Shannak K, Lac ST, Pristupa ZB, Dixon LM, Kish SJ (1994) Heterogeneous subregional binding patterns of 3H-WIN 35,428 and 3H-GBR 12,935 are differentially regulated by chronic cocaine self-administration. J Neurosci 14: 2966–2979PubMedGoogle Scholar
  60. Zelnik N, Angel I, Paul SM, Kleinman JE (1986) Decreased density of human striatal dopamine uptake sites with age. Eur J Pharmacol 126: 175–176PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 1997

Authors and Affiliations

  • T. Brücke
    • 1
    • 2
  • S. Asenbaum
    • 1
    • 2
  • W. Pirker
    • 1
  • S. Djamshidian
    • 1
  • S. Wenger
    • 1
  • Ch. Wöber
    • 1
  • Ch. Müller
    • 1
  • I. Podreka
    • 3
  1. 1.University Clinic for NeurologyViennaAustria
  2. 2.University Clinic for Nuclear MedicineViennaAustria
  3. 3.University Clinic for Rudolfstiftung HospitalViennaAustria

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