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Annals of Nuclear Medicine

, Volume 28, Issue 9, pp 874–879 | Cite as

Uneven age effects of [18F]FP-CIT binding in the striatum of Parkinson’s disease

  • Chong S. Lee
  • Su-Jeong Kim
  • Seung Jun Oh
  • Hye Ok Kim
  • Sung-Cheol Yun
  • Doris Doudet
  • Jae Seung KimEmail author
Original Article

Abstract

Objective

Dopamine transporter (DAT) imaging shows age-related decline of ligand binding in the normal striatum, a decline attributed to regulatory changes. We investigated if similar changes occur in the striatum of Parkinson’s disease (PD) patients, using PET and [18F]FP-CIT, a ligand for DAT.

Methods

We performed [18F]FP-CIT PET in 39 drug-naïve, de novo PD patients (age 56.0 ± 11.6 years, mean ± SD) and 34 healthy control subjects (age 52.3 ± 17.8). Parkinsonism was assessed by UPDRS III and Purdue pegboard. Binding ratios of [18F]FP-CIT were obtained in the putamen and caudate using the occipital cortex as reference.

Results

Mean [18F]FP-CIT binding ratios in PD were 3.76 ± 0.74 (mean ± SD) in the putamen and 6.80 ± 1.05 in the caudate nucleus, significantly smaller than those in the healthy control (9.20 ± 1.38, 8.66 ± 1.12, respectively; p < 0.001 vs. healthy control for both). Regression analysis of [18F]FP-CIT binding ratios on age in healthy subjects showed significant correlations in the putamen (p < 0.001) and caudate nucleus (p < 0.001). Similar analysis in PD patients also showed significant correlations in the putamen (p = 0.015) and caudate nucleus (p = 0.018). The slope of regression in the putamen was −0.061 in the healthy control and −0.017 in PD, with significant differences between the two groups (p = 0.0003). In contrast, the regression slope in the caudate nucleus was −0.040 in the healthy control group, and −0.032 in the PD group with no significant differences between the two groups.

Conclusions

Striatal [18F]FP-CIT binding showed significant age affects in patients with de novo PD after standardization for the severity of disease. The age effects were significantly smaller in PD patients than those in healthy subjects, but only in the putamen, not in the caudate nucleus. Given that age-related attrition of DA neurons is even in normal striatum, the uneven age effects in the parkinsonian striatum are likely to reflect the superimposition of disease-driven compensation on the aging effect.

Keywords

[18F]FP-CIT Positron emission tomography Age Dopamine transporter Parkinson’s disease 

Notes

Acknowledgments

The study was supported by Grants from the Korean government (MEST) (No. 2010-0020677) through the future based technology development program of the National Research Foundation.

Conflict of interest

None.

References

  1. 1.
    Martin WR, Palmer MR, Patlak CS, Calne DB. Nigrostriatal function in humans studied with positron emission tomography. Ann Neurol. 1989;26:535–42.PubMedCrossRefGoogle Scholar
  2. 2.
    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
  3. 3.
    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
  4. 4.
    Sawle GV, Colebatch JG, Shah A, Brooks DJ, Marsden CD, Frackowiak RS. Striatal function in normal aging: implications for Parkinson’s disease. Ann Neurol. 1990;28:799–804.PubMedCrossRefGoogle Scholar
  5. 5.
    Frey KA, Koeppe RA, Kilbourn MR, Vander Borght TM, Albin RL, Gilman S, et al. Presynaptic monoaminergic vesicles in Parkinson’s disease and normal aging. Ann Neurol. 1996;40:873–84.PubMedCrossRefGoogle Scholar
  6. 6.
    Ishikawa T, Dhawan V, Kazumata K, Chaly T, Mandel F, Neumeyer J, et al. Comparative nigrostriatal dopaminergic imaging with iodine-123-beta CIT-FP/SPECT and fluorine-18-FDOPA/PET. J Nucl Med. 1996;37:1760–5.PubMedGoogle Scholar
  7. 7.
    Troiano AR, Schulzer M, de la Fuente-Fernandez R, Mak E, McKenzie J, Sossi V, et al. Dopamine transporter PET in normal aging: dopamine transporter decline and its possible role in preservation of motor function. Synapse. 2010;64:146–51.PubMedCrossRefGoogle Scholar
  8. 8.
    Zahniser NR, Sorkin A. Rapid regulation of the dopamine transporter: role in stimulant addiction? Neuropharmacology. 2004;47(Suppl 1):80–91.PubMedCrossRefGoogle Scholar
  9. 9.
    Lee CS, Samii A, Sossi V, Ruth TJ, Schulzer M, Holden JE, et al. In vivo positron emission tomographic evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson’s disease. Ann Neurol. 2000;47:493–503.PubMedCrossRefGoogle Scholar
  10. 10.
    Salvatore MF, Apparsundaram S, Gerhardt GA. Decreased plasma membrane expression of striatal dopamine transporter in aging. Neurobiol Aging. 2003;24:1147–54.PubMedCrossRefGoogle Scholar
  11. 11.
    Tissingh G, Bergmans P, Booij J, Winogrodzka A, Stoof JC, Wolters EC, et al. [123I]beta-CIT single-photon emission tomography in Parkinson’s disease reveals a smaller decline in dopamine transporters with age than in controls. Eur J Nucl Med. 1997;24:1171–4.PubMedGoogle Scholar
  12. 12.
    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
  13. 13.
    Hornykiewicz O. Biochemical aspects of Parkinson’s disease. Neurology. 1998;51:S2–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Hughes AJ, Daniel SE, Blankson S, Lees AJ. A clinicopathologic study of 100 cases of Parkinson’s disease. Arch Neurol. 1993;50:140–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Roselli F, Pisciotta NM, Pennelli M, Aniello MS, Gigante A, De Caro MF, et al. Midbrain SERT in degenerative parkinsonisms: a 123I-FP-CIT SPECT study. Mov Disord. 2010;25:1853–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology. 1967;17:427–42.PubMedCrossRefGoogle Scholar
  17. 17.
    Lee SJ, Oh SJ, Chi DY, Kang SH, Kil HS, Kim JS, et al. One-step high-radiochemical-yield synthesis of [18F]FP-CIT using a protic solvent system. Nucl Med Biol. 2007;34:345–51.PubMedCrossRefGoogle Scholar
  18. 18.
    Oh M, Kim JS, Kim JY, Shin KH, Park SH, Kim HO, Moon DH, Oh SJ, Chung SJ, Lee CS. Subregional patterns of preferential striatal dopamine transporter loss differ in Parkinson disease, progressive supranuclear palsy, and multiple-system atrophy. J Nucl Med. 2012;53(3):399–406.PubMedCrossRefGoogle Scholar
  19. 19.
    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.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Vingerhoets FJ, Snow BJ, Schulzer M, Morrison S, Ruth TJ, Holden JE, Cooper S, Calne DB. Reproducibility of fluorine-18-6-fluorodopa positron emission tomography in normal human subjects. J Nucl Med. 1994;35(1):18–24.PubMedGoogle Scholar
  21. 21.
    Wullner U, Pakzaban P, Brownell AL, Hantraye P, Burns L, Shoup T, et al. Dopamine terminal loss and onset of motor symptoms in MPTP-treated monkeys: a positron emission tomography study with 11C-CFT. Exp Neurol. 1994;126:305–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Booij J, Bergmans P, Winogrodzka A, Speelman JD, Wolters EC. Imaging of dopamine transporters with [123I]FP-CIT SPECT does not suggest a significant effect of age on the symptomatic threshold of disease in Parkinson’s disease. Synapse. 2001;39:101–8.PubMedCrossRefGoogle Scholar
  23. 23.
    De La Fuente-Fernandez R, Lim AS, Sossi V, Adam MJ, Ruth TJ, Calne DB, et al. Age and severity of nigrostriatal damage at onset of Parkinson’s disease. Synapse. 2003;47:152–8.CrossRefGoogle Scholar
  24. 24.
    de la Fuente-Fernandez R, Schulzer M, Kuramoto L, Cragg J, Ramachandiran N, Au WL, et al. Age-specific progression of nigrostriatal dysfunction in Parkinson’s disease. Ann Neurol. 2011;69:803–10.PubMedCrossRefGoogle Scholar
  25. 25.
    Wilson JM, Levey AI, Rajput A, Ang L, Guttman M, Shannak K, et al. Differential changes in neurochemical markers of striatal dopamine nerve terminals in idiopathic Parkinson’s disease. Neurology. 1996;47:718–26.PubMedCrossRefGoogle Scholar
  26. 26.
    Kish SJ, Shannak K, Rajput A, Deck JH, Hornykiewicz O. Aging produces a specific pattern of striatal dopamine loss: implications for the etiology of idiopathic Parkinson’s disease. J Neurochem. 1992;58:642–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Ishibashi K, Ishii K, Oda K, Kawasaki K, Mizusawa H, Ishiwata K. Regional analysis of age-related in dopamine transporters and dopamine D2-like receptors in human striatum. Synapse. 2009;63:282–90.PubMedCrossRefGoogle Scholar
  28. 28.
    Wilson JM, Kish SJ. The vesicular monoamine transporter, in contrast to the dopamine transporter, is not altered by chronic cocaine self-administration in the rat. J Neurosci. 1996;16:3507–10.PubMedGoogle Scholar
  29. 29.
    Afonso-Oramas D, Cruz-Muros I, Barroso-Chinea P, Alvarez de la Rosa D, Castro-Hernandez J, Salas-Hernandez J, et al. The dopamine transporter is differentially regulated after dopaminergic lesion. Neurobiol Dis. 2010;40:518–30.PubMedCrossRefGoogle Scholar
  30. 30.
    Bannon MJ, Whitty CJ. Age-related and regional differences in dopamine transporter mRNA expression in human midbrain. Neurology. 1997;48:969–77.PubMedCrossRefGoogle Scholar
  31. 31.
    Cruz-Muros I, Afonso-Oramas D, Abreu P, Perez-Delgado MM, Rodriguez M, Gonzalez-Hernandez T. Aging effects on the dopamine transporter expression and compensatory mechanisms. Neurobiol Aging. 2009;30:973–86.PubMedCrossRefGoogle Scholar
  32. 32.
    Marek K, Jennings D, Seibyl J. Single-photon emission tomography and dopamine transporter imaging in Parkinson’s disease. Adv Neurol. 2003;91:183–91.PubMedGoogle Scholar
  33. 33.
    Bedard P, Larochelle L, Parent A, Poirier LJ. The nigrostriatal pathway: a correlative study based on neuroanatomical and neurochemical criteria in the cat and the monkey. Exp Neurol. 1969;25:365–77.PubMedCrossRefGoogle Scholar

Copyright information

© The Japanese Society of Nuclear Medicine 2014

Authors and Affiliations

  • Chong S. Lee
    • 1
  • Su-Jeong Kim
    • 1
  • Seung Jun Oh
    • 2
  • Hye Ok Kim
    • 2
  • Sung-Cheol Yun
    • 3
  • Doris Doudet
    • 4
  • Jae Seung Kim
    • 2
    Email author
  1. 1.Department of NeurologyAsan Medical Center, University of Ulsan College of MedicineSeoulKorea
  2. 2.Department of Nuclear Medicine, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea
  3. 3.Department of Clinical Epidemiology and BiostatisticsAsan Medical Center, University of Ulsan College of MedicineSeoulKorea
  4. 4.Department of Medicine/NeurologyUniversity of British ColumbiaVancouverCanada

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