Europe PMC

This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our privacy notice and cookie policy.

Dopamine transporter imaging with [123I]-beta-CIT demonstrates presynaptic nigrostriatal dopaminergic damage in Wilson's disease.

Author information

Affiliations

  • 1. Department of Neurology and Nuclear Medicine, College of Medicine, Seoul National University, Seoul National University Hospital, Korea.
      Authors
    • Jeon B 1
    (1 author)

Journal of Neurology, Neurosurgery, and Psychiatry, 01 Jul 1998, 65(1):60-64
https://doi.org/10.1136/jnnp.65.1.60 PMID: 9667562 PMCID: PMC2170169

Free full text in Europe PMC

Abstract 

Objectives

The most common neurological manifestations in Wilson's disease are parkinsonism and dystonia. These are assumed to be due to striatal injury, which has been repeatedly demonstrated by pathology and CT or MRI. The substantia nigra has not been shown to be damaged in pathological studies. However, there have been clinical and imaging studies suggesting presynaptic nigrostriatal injury. (1r)-2Beta-carbomethoxy-3beta-(4-iodophenyl)tropane (beta-CIT) is a specific ligand that binds to the dopamine transporter (DAT), and can examine the integrity of dopaminergic nerve terminals. Evidence for presynaptic nigrostriatal dopaminergic damage in Wilson's disease was searched for using [123I]-beta-CIT SPECT.

Methods

Six patients with Wilson's disease were studied, together with 15 healthy normal controls, and six patients with Parkinson's disease. After injection of [123I]-beta-CIT, SPECT studies were done at 18 hours. Specific striatal/occipital binding ratio (S/O ratio) was calculated as (striatal binding-occipital binding)/occipital binding.

Results

The specific S/O ratios were 6.22 (1.32) (mean (SD)) in normal volunteers, 3.78 (0.65) in Parkinson's disease, and 3.60 (0.49) in Wilson's disease.

Conclusion

There was severe loss of the DAT in the striatum suggesting significant damage in presynaptic nigrostriatal dopaminergic nerve terminals. Therefore, a presynaptic lesion may contribute to neurological manifestations in Wilson's disease.

Free full text 

Logo of jnnpsycLink to Publisher's site
J Neurol Neurosurg Psychiatry. 1998 Jul; 65(1): 60–64.
PMCID: PMC2170169
PMID: 9667562

Dopamine transporter imaging with [123I]-β-CIT demonstrates presynaptic nigrostriatal dopaminergic damage in Wilson's disease

B Jeon, J Kim, J Jeong, K Kim, Y Chang, D Lee, and M Lee
Author information Copyright and License information Disclaimer

Abstract

OBJECTIVES—The most common neurological manifestations in Wilson's disease are parkinsonism and dystonia. These are assumed to be due to striatal injury, which has been repeatedly demonstrated by pathology and CT or MRI. The substantia nigra has not been shown to be damaged in pathological studies. However, there have been clinical and imaging studies suggesting presynaptic nigrostriatal injury. (1r)-2β-carbomethoxy-3β-(4-iodophenyl)tropane (β-CIT) is a specific ligand that binds to the dopamine transporter (DAT), and can examine the integrity of dopaminergic nerve terminals. Evidence for presynaptic nigrostriatal dopaminergic damage in Wilson's disease was searched for using [123I]-β-CIT SPECT.
METHODS—Six patients with Wilson's disease were studied, together with 15 healthy normal controls, and six patients with Parkinson's disease. After injection of [123I]-β-CIT, SPECT studies were done at 18 hours. Specific striatal/occipital binding ratio (S/O ratio) was calculated as (striatal binding−occipital binding)/occipital binding.
RESULTS—The specific S/O ratios were 6.22 (1.32) (mean (SD)) in normal volunteers, 3.78 (0.65) in Parkinson's disease, and 3.60 (0.49) in Wilson's disease.
CONCLUSION—There was severe loss of the DAT in the striatum suggesting significant damage in presynaptic nigrostriatal dopaminergic nerve terminals. Therefore, a presynaptic lesion may contribute to neurological manifestations in Wilson's disease.

Full Text

The Full Text of this article is available as a PDF (137K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Williams FJ, Walshe JM. Wilson's disease. An analysis of the cranial computerized tomographic appearances found in 60 patients and the changes in response to treatment with chelating agents. Brain. 1981 Dec;104(Pt 4):735–752. [Abstract] [Google Scholar]
  • Kendall BE, Pollock SS, Bass NM, Valentine AR. Wilson's disease. Clinical correction with cranial computed tomography. Neuroradiology. 1981;22(1):1–5. [Abstract] [Google Scholar]
  • Prayer L, Wimberger D, Kramer J, Grimm G, Oder W, Imhof H. Cranial MRI in Wilson's disease. Neuroradiology. 1990;32(3):211–214. [Abstract] [Google Scholar]
  • Roh JK, Lee TG, Wie BA, Lee SB, Park SH, Chang KH. Initial and follow-up brain MRI findings and correlation with the clinical course in Wilson's disease. Neurology. 1994 Jun;44(6):1064–1068. [Abstract] [Google Scholar]
  • Aisen AM, Martel W, Gabrielsen TO, Glazer GM, Brewer G, Young AB, Hill G. Wilson disease of the brain: MR imaging. Radiology. 1985 Oct;157(1):137–141. [Abstract] [Google Scholar]
  • Yuh WT, Flickinger FW. Unusual MR findings in CNS Wilson disease. AJR Am J Roentgenol. 1988 Oct;151(4):834–834. [Abstract] [Google Scholar]
  • Oertel WH, Tatsch K, Schwarz J, Kraft E, Trenkwalder C, Scherer J, Weinzierl M, Vogl T, Kirsch CM. Decrease of D2 receptors indicated by 123I-iodobenzamide single-photon emission computed tomography relates to neurological deficit in treated Wilson's disease. Ann Neurol. 1992 Dec;32(6):743–748. [Abstract] [Google Scholar]
  • Westermark K, Tedroff J, Thuomas KA, Hartvig P, Långström B, Andersson Y, Hörnfeldt K, Aquilonius SM. Neurological Wilson's disease studied with magnetic resonance imaging and with positron emission tomography using dopaminergic markers. Mov Disord. 1995 Sep;10(5):596–603. [Abstract] [Google Scholar]
  • Morgan JP, Preziosi TJ, Bianchine JR. Ineffectiveness of L-dopa as supplement to penicillamine in a case of Wilson's disease. Lancet. 1970 Sep 26;2(7674):659–659. [Abstract] [Google Scholar]
  • Nyberg P, Gottfries CG, Holmgren G, Persson S, Roos BE, Winblad B. Advanced catecholaminergic disturbances in the brain in a case of Wilson's disease. Acta Neurol Scand. 1982 Jan;65(1):71–75. [Abstract] [Google Scholar]
  • Barbeau A, Friesen H. Treatment of Wilson's disease with L-dopa after failure with penicillamine. Lancet. 1970 May 30;1(7657):1180–1181. [Abstract] [Google Scholar]
  • Snow BJ, Bhatt M, Martin WR, Li D, Calne DB. The nigrostriatal dopaminergic pathway in Wilson's disease studied with positron emission tomography. J Neurol Neurosurg Psychiatry. 1991 Jan;54(1):12–17. [Europe PMC free article] [Abstract] [Google Scholar]
  • Uhl GR. Neurotransmitter transporters (plus): a promising new gene family. Trends Neurosci. 1992 Jul;15(7):265–268. [Abstract] [Google Scholar]
  • Laruelle M, Baldwin RM, Malison RT, Zea-Ponce Y, Zoghbi SS, al-Tikriti MS, Sybirska EH, Zimmermann RC, Wisniewski G, Neumeyer JL, et al. SPECT imaging of dopamine and serotonin transporters with [123I]beta-CIT: pharmacological characterization of brain uptake in nonhuman primates. Synapse. 1993 Apr;13(4):295–309. [Abstract] [Google Scholar]
  • Zea-Ponce Y, Baldwin RM, Laruelle M, Wang S, Neumeyer JL, Innis RB. Simplified multidose preparation of iodine-123-beta-CIT: a marker for dopamine transporters. J Nucl Med. 1995 Mar;36(3):525–529. [Abstract] [Google Scholar]
  • Volkow ND, Ding YS, Fowler JS, Wang GJ, Logan J, Gatley SJ, Hitzemann R, Smith G, Fields SD, Gur R. Dopamine transporters decrease with age. J Nucl Med. 1996 Apr;37(4):554–559. [Abstract] [Google Scholar]
  • Marek KL, Seibyl JP, Zoghbi SS, Zea-Ponce Y, Baldwin RM, Fussell B, Charney DS, van Dyck C, Hoffer PB, Innis RP. [123I] beta-CIT/SPECT imaging demonstrates bilateral loss of dopamine transporters in hemi-Parkinson's disease. Neurology. 1996 Jan;46(1):231–237. [Abstract] [Google Scholar]
  • Vander Borght T, Kilbourn M, Desmond T, Kuhl D, Frey K. The vesicular monoamine transporter is not regulated by dopaminergic drug treatments. Eur J Pharmacol. 1995 Dec 29;294(2-3):577–583. [Abstract] [Google Scholar]
  • Kilbourn MR, Sherman PS, Pisani T. Repeated reserpine administration reduces in vivo [18F]GBR 13119 binding to the dopamine uptake site. Eur J Pharmacol. 1992 May 27;216(1):109–112. [Abstract] [Google Scholar]
  • Wilson JM, Nobrega JN, Carroll ME, Niznik HB, Shannak K, Lac ST, Pristupa ZB, Dixon LM, Kish SJ. Heterogeneous subregional binding patterns of 3H-WIN 35,428 and 3H-GBR 12,935 are differentially regulated by chronic cocaine self-administration. J Neurosci. 1994 May;14(5 Pt 2):2966–2979. [Abstract] [Google Scholar]
  • Perrone-Capano C, Tino A, Amadoro G, Pernas-Alonso R, di Porzio U. Dopamine transporter gene expression in rat mesencephalic dopaminergic neurons is increased by direct interaction with target striatal cells in vitro. Brain Res Mol Brain Res. 1996 Jul;39(1-2):160–166. [Abstract] [Google Scholar]
  • Przedborski S, Kostic V, Jackson-Lewis V, Cadet JL, Burke RE. Effect of unilateral perinatal hypoxic-ischemic brain injury in the rat on dopamine D1 and D2 receptors and uptake sites: a quantitative autoradiographic study. J Neurochem. 1991 Dec;57(6):1951–1961. [Abstract] [Google Scholar]
  • Burke RE, Kent J, Kenyon N, Karanas A. Unilateral hypoxic-ischemic injury in neonatal rat results in a persistent increase in the density of striatal tyrosine hydroxylase immunoperoxidase staining. Brain Res Dev Brain Res. 1991 Feb 22;58(2):171–179. [Abstract] [Google Scholar]
  • Burke RE, Reches A. Preserved striatal tyrosine hydroxylase activity, assessed in vivo, following neonatal hypoxia-ischemia. Brain Res Dev Brain Res. 1991 Aug 19;61(2):277–280. [Abstract] [Google Scholar]
  • Schwarcz R, Whetsell WO, Jr, Mangano RM. Quinolinic acid: an endogenous metabolite that produces axon-sparing lesions in rat brain. Science. 1983 Jan 21;219(4582):316–318. [Abstract] [Google Scholar]
  • Schwarcz R, Hökfelt T, Fuxe K, Jonsson G, Goldstein M, Terenius L. Ibotenic acid-induced neuronal degeneration: a morphological and neurochemical study. Exp Brain Res. 1979 Oct;37(2):199–216. [Abstract] [Google Scholar]
Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

Full text links 

Read article at publisher's site: https://doi.org/10.1136/jnnp.65.1.60

Read article for free, from open access legal sources, via Unpaywall: https://jnnp.bmj.com/content/jnnp/65/1/60.full.pdfUnpaywall

Citations & impact 

Impact metrics

46
Citations
Jump to Citations

Citations of article over time

Alternative metrics

Altmetric item for https://www.altmetric.com/details/112816692
Altmetric
Discover the attention surrounding your research
https://www.altmetric.com/details/112816692

Smart citations by scite.ai
Smart citations by scite.ai include citation statements extracted from the full text of the citing article. The number of the statements may be higher than the number of citations provided by EuropePMC if one paper cites another multiple times or lower if scite has not yet processed some of the citing articles.
Explore citation contexts and check if this article has been supported or disputed.
https://scite.ai/reports/10.1136/jnnp.65.1.60

Supporting
Mentioning
Contrasting
0
53
0

Article citations

Go to all (46) article citations

Similar Articles 

To arrive at the top five similar articles we use a word-weighted algorithm to compare words from the Title and Abstract of each citation.