Nuclear Medicine and Molecular Imaging

The Korean Society of Nuclear Medicine (대한핵의학회)
권호 표지

Imaging of Dopaminergic System in Movement Disorders

이상운동질환에서의 도파민 신경계 영상

  • Kim, Yu-Kyeong (Department of Nuclear Medicine, Seoul National University College of Medicine) ;
  • Kim, Sang-Eun (Department of Nuclear Medicine, Seoul National University College of Medicine)
  • 김유경 (서울대학교 의과대학 핵의학교실) ;
  • 김상은 (서울대학교 의과대학 핵의학교실)
  • Published : 2007.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

Parkinson's disease is a common neurodegenerative disorder that is mainly caused by dopaminergic neuron loss in the substantia nigra. Several radiopharmaceutics have been developed to evaluate the integrity of dopaminergic neuronal system. In vivo PET and SPECT imaging of presynaptic dopamine imaing are already applied to Parkinson's disease and other parkinsonism, and can demonstrate the dopaminergic dysfunction. This review summarized the use of the presynaptic dopaminergic imaging in PD as biomarkers in evaluation of disease progression as well as in diagnosis of PD.

Keywords

References

  1. Biomarkers Definitions Working Group. Biomarkers and surrogate end-points; preferred definitions and conceptual framework. Clini Pharmacol Ther 2001;69:89-95 https://doi.org/10.1067/mcp.2001.113989
  2. Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F. Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J Neurol Sci 1973;20:415-55 https://doi.org/10.1016/0022-510X(73)90175-5
  3. Pate BD, Kawamata T, Yamada T, McGeer EG, Hewitt KA, Snow BJ, et al. Correlation of striatal fluorodopa uptake in the MPTP monkey with dopaminergic indices. Ann Neurol 1993;34:331-8 https://doi.org/10.1002/ana.410340306
  4. Snow BJ, Tooyama I, McGeer EG, Yamada T, Calne DB, Takahashi H, et al. Human positron emission tomographic [$^{18}F$]fluorodopa studies correlate with dopamine cell counts and levels. Ann Neurol 1993;34:324-30
  5. Barrio JR, Huang SC, Phelps ME. Biological imaging and the molecular basis of dopaminergic diseases. Biochem Pharmacol 1997;54:341-8 https://doi.org/10.1016/S0006-2952(97)00031-2
  6. Tedroff J, Ekesbo A, Rydin E, Langstrom B, Hagberg G. Regulation of dopaminergic activity in early Parkinson's disease. Ann Neurol 1999;46:359-65 https://doi.org/10.1002/1531-8249(199909)46:3<359::AID-ANA11>3.0.CO;2-G
  7. Zhu MY, Juorio AV, Paterson IA, Boulton AA. Regulation of aromatic L-amino acid decarboxylase in rat striatal synaptosomes: effects of dopamine receptor agonists and antagonists. Br J Pharmacol 1994;112:23-30 https://doi.org/10.1111/j.1476-5381.1994.tb13023.x
  8. Gjedde A, Leger GC, Cumming P, Yasuhara Y, Evans AC, Guttman M, et al. Striatal L-dopa decarboxylase activity in Parkinson's disease in vivo: implications for the regulation of dopamine synthesis. J Neurochem 1993;61: 1538-41 https://doi.org/10.1111/j.1471-4159.1993.tb13651.x
  9. 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;294:577-83 https://doi.org/10.1016/0014-2999(95)00594-3
  10. Naudon L, Leroux-Nicollet I, Costentin J. Short-term treatments with haloperidol or bromocriptine do not alter the density of the monoamine vesicular transporter in the substantia nigra. Neurosci Lett 1994;173:1-4 https://doi.org/10.1016/0304-3940(94)90136-8
  11. 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 https://doi.org/10.1523/JNEUROSCI.16-10-03507.1996
  12. Booij J, Tissingh G, Winogrodzka A, van Royen EA. Imaging of the dopaminergic neurotransmission system using single-photon emission tomography and positron emission tomography in patients with parkinsonism. Eur J Nucl Med 1999;26:171-82 https://doi.org/10.1007/s002590050374
  13. Seibyl JP, Marek KL, Quinlan D, Sheff K, Zoghbi S, Zea-Ponce Y, Baldwin RM, Fussell B, Smith EO, Charney DS, et al. Decreased single-photon emission computed tomographic [$^{123}I$]beta-CIT striatal uptake correlates with symptom severity in Parkinson's disease. Ann Neurol 1995;38:589-98 https://doi.org/10.1002/ana.410380407
  14. Parkinson Study Group. A multicenter assessment of dopamine transporter imaging with DOPASCAN/SPECT in parkinsonism. Neurology 2000;55:1540-7 https://doi.org/10.1212/WNL.55.10.1540
  15. Jennings DL, Seibyl JP, Oakes D, Eberly S, Murphy J, Marek K. [$^{123}I$] beta-CIT and single-photon emission computed tomographic imaging vs clinical evaluation in Parkinsonian syndrome: unmasking an early diagnosis. Arch Neurol 2004;61:1224-9 https://doi.org/10.1001/archneur.61.8.1224
  16. Brucke T, Asenbaum S, Pirker W, Djamshidian S, Wenger S, Wober C, et al. Measurement of the dopaminergic degeneration in Parkinson's disease with [$^{123}I$] beta-CIT and SPECT. Correlation with clinical findings and comparison with multiple system atrophy and progressive supranuclear palsy. J Neural Transm Suppl 1997; 50:9-24
  17. 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 [$^{123}I$]-FP-CIT SPECT imaging: the [$^{123}I$]-FP-CIT study group. Mov Disord 2000;15: 503-10 https://doi.org/10.1002/1531-8257(200005)15:3<503::AID-MDS1013>3.0.CO;2-V
  18. Benamer HT, Patterson J, Wyper DJ, Hadley DM, Macphee GJ, Grosset DG. Correlation of Parkinson's disease severity and duration with 123I-FP-CIT SPECT striatal uptake. Mov Disord 2000;15:692-8 https://doi.org/10.1002/1531-8257(200007)15:4<692::AID-MDS1014>3.0.CO;2-V
  19. Seibyl JP, Marek K, Sheff K, Zoghbi S, Baldwin RM, Charney DS, et al. Iodine-123-beta-CIT and iodine-123-FPCIT SPECT measurement of dopamine transporters in healthy subjects and Parkinson's patients. J Nucl Med 1998;39:1500-8
  20. Rinne JO, Ruottinen H, Bergman J, Haaparanta M, Sonninen P, Solin O. Usefulness of a dopamine transporter PET ligand [(18)F]beta-CFT in assessing disability in Parkinson's disease. J Neurol Neurosurg Psychiatry 1999;67:737-41 https://doi.org/10.1136/jnnp.67.6.737
  21. Nurmi E, Ruottinen HM, Kaasinen V, Bergman J, Haaparanta M, Solin O, et al. Progression in Parkinson's disease: a positron emission tomography study with a dopamine transporter ligand [$^{18}F$]CFT. Ann Neurol 2000;47:804-8 https://doi.org/10.1002/1531-8249(200006)47:6<804::AID-ANA14>3.0.CO;2-F
  22. Kung HF, Kim HJ, Kung MP, Meegalla SK, Plossl K, Lee HK. Imaging of dopamine transporters in humans with technetium-99m TRODAT-1. Eur J Nucl Med 1996;23:1527-30 https://doi.org/10.1007/BF01254479
  23. Choi SR, Kung MP, Plossl K, Meegalla S, Kung HF. An improved kit formulation of a dopamine transporter imaging agent: [Tc-99m]TRODAT-1. Nucl Med Biol 1999;26:461-6 https://doi.org/10.1016/S0969-8051(99)00010-4
  24. Zigmond MJ, Abercrombie ED, Berger TW, Grace AA, Stricker EM. Compensations after lesions of central dopaminergic neurons: some clinical and basic implications. Trends Neurosci 1990; 13: 290-6 https://doi.org/10.1016/0166-2236(90)90112-N
  25. 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 https://doi.org/10.1002/1531-8249(200004)47:4<493::AID-ANA13>3.0.CO;2-4
  26. Huang WS, Lin SZ, Lin JC, Wey SP, Ting G, Liu RS. Evaluation of early-stage Parkinson's disease with 99mTc-TRODAT-1 imaging. J Nucl Med 2001;42:1303-8
  27. Huang WS, Lee MS, Lin JC, Chen CY, Yang YW, Lin SZ, Wey SP. Usefulness of brain 99mTc-TRODAT-1 SPET for the evaluation of Parkinson's disease. Eur J Nucl Med Mol Imaging 2004;31:155-61 https://doi.org/10.1007/s00259-003-1331-x
  28. Van Laere K, De Ceuninck L, Dom R, Van den Eynden J, Vanbilloen H, Cleynhens J, Dupont P, Bormans G, Verbruggen A, Mortelmans L. Dopamine transporter SPECT using fast kinetic ligands: $^{123}I$-FP-beta-CIT versus $^{99m}Tc$-TRODAT-1. Eur J Nucl Med Mol Imaging 2004;31:1119-27 https://doi.org/10.1007/s00259-004-1480-6
  29. Huang WS, Chiang YH, Lin JC, Chou YH, Cheng CY, Liu RS. Crossover study of $^{99m}Tc$-TRODAT-1 SPECT and $^{18}F$-FDOPA PET in Parkinson's disease patients. J Nucl Med 2003;44:999-1005
  30. Schwarz J, Linke R, Kerner M, Mozley PD, Trenkwalder C, Gasser T, Tatsch K. Striatal dopamine transporter binding assessed by [I-123]IPT and single photon emission computed tomography in patients with early Parkinson's disease: implications for a preclinical diagnosis. Arch Neurol 2000;57:205-8 https://doi.org/10.1001/archneur.57.2.205
  31. 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 Neurosurg Psychiatry 1992;55:181-4 https://doi.org/10.1136/jnnp.55.3.181
  32. Meara J, Bhowmick BK, Hobson P. Accuracy of diagnosis in patients with presumed Parkinson's disease. Age Ageing 1999;28:99-102 https://doi.org/10.1093/ageing/28.2.99
  33. Morrish PK, Sawle GV, Brooks DJ. An [$^{18}F$]dopa-PET and clinical study of the rate of progression in Parkinson's disease. Brain 1996; 119: 585-91 https://doi.org/10.1093/brain/119.2.585
  34. Hornykiewicz O. Biochemical aspects of Parkinson's disease. Neurology 1998;51:S2-9
  35. loss in the striatum of patients with idiopathic Parkinson's disease. Pathophysiologic and clinical implications. N Engl J Med 1988;318:876-80 https://doi.org/10.1056/NEJM198804073181402
  36. Damier P, Hirsch EC, Agid Y, Graybiel AM. The substantia nigra of the human brain. II. Patterns of loss of dopamine-containing neurons in Parkinson's disease. Brain 1999;122:1437-48 https://doi.org/10.1093/brain/122.8.1437
  37. Brooks DJ, Frey KA, Marek KL, Oakes D, Paty D, Prentice R, et al. Assessment of neuroimaging techniques as biomarkers of the progression of Parkinson's disease. Exp Neurol 2003;184 Suppl 1:S68-79 https://doi.org/10.1016/j.expneurol.2003.08.008
  38. Morrish PK. How valid is dopamine transporter imaging as a surrogate marker in research trials in Parkinson's disease? Mov Disord 2003;18 Suppl 7:S63-70 https://doi.org/10.1002/mds.10565
  39. Vingerhoets FJ, Snow BJ, Lee CS, Schulzer M, Mak E, Calne DB. Longitudinal fluorodopa positron emission tomographic studies of the evolution of idiopathic parkinsonism. Ann Neurol 1994;36: 759-64 https://doi.org/10.1002/ana.410360512
  40. Nurmi E, Ruottinen HM, Bergman J, Haaparanta M, Solin O, Sonninen P, Rinne JO. Rate of progression in Parkinson's disease: a 6-[$^{18}F$]fluoro-L-dopa PET study. Mov Disord 2001;16:608-15 https://doi.org/10.1002/mds.1139
  41. van Dyck CH, Seibyl JP, Malison RT, Laruelle M, Zoghbi SS, Baldwin RM, Innis RB. Age-related decline in dopamine transporters: analysis of striatal subregions, nonlinear effects, and hemispheric asymmetries. Am J Geriatr Psychiatry 2002;10:36-43 https://doi.org/10.1097/00019442-200201000-00005
  42. Marek K, Innis R, van Dyck C, Fussell B, Early M, Eberly S, et al. [$^{123}I$]beta-CIT SPECT imaging assessment of the rate of Parkinson's disease progression. Neurology 2001;57:2089-94 https://doi.org/10.1212/WNL.57.11.2089
  43. Pirker W, Holler I, Gerschlager W, Asenbaum S, Zettinig G, Brucke T. Measuring the rate of progression of Parkinson's disease over a 5-year period with beta-CIT SPECT. Mov Disord 2003; 18:1266-72 https://doi.org/10.1002/mds.10531
  44. Fearnley JM, Lees AJ. Ageing and Parkinson's disease: substantia nigra regional selectivity. Brain 1991; 114: 2283-301 https://doi.org/10.1093/brain/114.5.2283
  45. McGeer PL, Itagaki S, Akiyama H, McGeer EG. Rate of cell death in parkinsonism indicates active neuropathological process. Ann Neurol 1988;24:574-6 https://doi.org/10.1002/ana.410240415
  46. Morrish PK, Rakshi JS, Bailey DL, Sawle GV, Brooks DJ. Measuring the rate of progression and estimating the preclinical period of Parkinson's disease with [18F]dopa PET. J Neurol Neurosurg Psychiatry 1998;64:314-9 https://doi.org/10.1136/jnnp.64.3.314
  47. Pirker W, Djamshidian S, Asenbaum S, Gerschlager W, Tribl G, Hoffmann M, Brucke T. Progression of dopaminergic degeneration in Parkinson's disease and atypical parkinsonism: a longitudinal beta-CIT SPECT study. Mov Disord 2002;17:45-53 https://doi.org/10.1002/mds.1265
  48. Moody CA, Granneman JG, Bannon MJ. Dopamine transporter binding in rat striatum and nucleus accumbens is unaltered following chronic changes in dopamine levels. Neurosci Lett 1996; 217:55-7 https://doi.org/10.1016/0304-3940(96)13048-2
  49. Gordon I, Weizman R, Rehavi M. Modulatory effect of agents active in the presynaptic dopaminergic system on the striatal dopamine transporter. Eur J Pharmacol 1996;298:27-30 https://doi.org/10.1016/0014-2999(95)00770-9
  50. Kilbourn MR, Frey KA, Vander Borght T, Sherman PS. Effects of dopaminergic drug treatments on in vivo radioligand binding to brain vesicular monoamine transporters. Nucl Med Biol 1996;23: 467-71 https://doi.org/10.1016/0969-8051(96)00023-6
  51. Innis RB, Marek KL, Sheff K, Zoghbi S, Castronuovo J, Feigin A, Seibyl JP. Effect of treatment with L-dopa/carbidopa or L-selegiline on striatal dopamine transporter SPECT imaging with [$^{123}I$]beta-CIT. Mov Disord 1999;14:436-42 https://doi.org/10.1002/1531-8257(199905)14:3<436::AID-MDS1008>3.0.CO;2-J
  52. Parkinson Study Group. A randomized controlled trial comparing pramipexole with levodopa in early Parkinson's disease: design and methods of the CALM-PD Study. Clin Neuropharmacol 2000;23: 34-44 https://doi.org/10.1097/00002826-200001000-00007
  53. Fahn S. Parkinson disease, the effect of levodopa, and the ELLDOPA trial. Earlier vs Later L-DOPA. Arch Neurol 1999;56: 529-35 https://doi.org/10.1001/archneur.56.5.529
  54. 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 https://doi.org/10.1002/ana.10609
  55. Fahn S, Oakes D, Shoulson I, Kieburtz K, Rudolph A, Lang A, Olanow CW, Tanner C, Marek K. Levodopa and the progression of Parkinson's disease. N Engl J Med 2004;351:2498-508 https://doi.org/10.1056/NEJMoa033447
  56. Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression. Jama 2002;287:1653-61 https://doi.org/10.1001/jama.287.13.1653
  57. Ravina B, Eidelberg D, Ahlskog JE, Albin RL, Brooks DJ, Carbon M, et al. The role of radiotracer imaging in Parkinson disease. Neurology 2005;64:208-15 https://doi.org/10.1212/01.WNL.0000149403.14458.7F
  58. Lokkegaard A, Werdelin LM, Regeur L, Karlsborg M, Jensen SR, Brodsgaard E, et al. Dopamine transporter imaging and the effects of deep brain stimulation in patients with Parkinson's disease. Eur J Nucl Med Mol Imaging 2007;34:508-16 https://doi.org/10.1007/s00259-006-0257-5
  59. Nakamura T, Dhawan V, Chaly T, Fukuda M, Ma Y, Breeze R, Greene P, Fahn S, Freed C, Eidelberg D. Blinded positron emission tomography study of dopamine cell implantation for Parkinson's disease. Ann Neurol 2001;50:181-7 https://doi.org/10.1002/ana.1075
  60. Olanow CW, Goetz CG, Kordower JH, Stoessl AJ, Sossi V, Brin MF, et al. A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson's disease. Ann Neurol 2003;54:403-14 https://doi.org/10.1002/ana.10720
  61. Neumeyer JL, Tamagnan G, Wang S, Gao Y, Milius RA, Kula NS, et al. N-substituted analogs of 2 beta-carbomethoxy-3 beta- (4'-iodophenyl)tropane (beta-CIT) with selective affinity to dopamine or serotonin transporters in rat forebrain. J Med Chem 1996;39:543-8 https://doi.org/10.1021/jm9505324
  62. Okada T, Fujita M, Shimada S, Sato K, Schloss P, Watanabe Y, et al. Assessment of affinities of beta-CIT, beta-CIT-FE, and beta-CIT-FP for monoamine transporters permanently expressed in cell lines. Nucl Med Biol 1998;25:53-8 https://doi.org/10.1016/S0969-8051(97)00156-X
  63. Ritz MC, Cone EJ, Kuhar MJ. Cocaine inhibition of ligand binding at dopamine, norepinephrine and serotonin transporters: a structure-activity study. Life Sci. 1990;46:635-45 https://doi.org/10.1016/0024-3205(90)90132-B
  64. Logan J, Fowler JS, Volkow ND, Wolf AP, Dewey SL, Schlyer DJ, et al. Graphical analysis of reversible radioligand binding from time-activity measurements applied to [N-11C-methyl]-(-)-cocaine PET studies in human subjects. J Cereb Blood Flow Metab. 1990;10(5):740-7 https://doi.org/10.1038/jcbfm.1990.127
  65. Telang FW, Volkow ND, Levy A, Logan J, Fowler JS, Felder C et al. Distribution of tracer levels of cocaine in the human brain as assessed with averaged [$^{11}C$] cocaine images. Synapse. 1999;31(4): 290-6 https://doi.org/10.1002/(SICI)1098-2396(19990315)31:4<290::AID-SYN7>3.0.CO;2-G
  66. Gatley SJ, Ding YS, Volkow ND, Chen R, Sugano Y, Fowler JS. Binding of d-threo-[$^{11}C$]methylphenidate to the dopamine transporter in vivo: insensitivity to synaptic dopamine. Eur J Pharmacol. 1995;281:141-9 https://doi.org/10.1016/0014-2999(95)00233-B
  67. Neumeyer JL, Tamagnan G, Wang S, Gao Y, Milius RA, Kula NS, et al. N-substituted analogs of 2 beta-carbomethoxy-3 beta- (4'-iodophenyl)tropane (beta-CIT) with selective affinity to dopamine or serotonin transporters in rat forebrain. J Med Chem 1996;39:543-8 https://doi.org/10.1021/jm9505324
  68. Madras BK, Meltzer PC, Liang AY, Elmaleh DR, Babich J, Fischman AJ. Altropane, a SPECT or PET imaging probe for dopamine neurons: I. Dopamine transporter binding in primate brain. Synapse 1998; 29: 93-104 https://doi.org/10.1002/(SICI)1098-2396(199806)29:2<93::AID-SYN1>3.0.CO;2-5
  69. Halldin C, Erixon-Lindroth N, Pauli S, Chou YH, Okubo Y, Karlsson P, et al. [$^{11}C$]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain. Eur J Nucl Med Mol Imaging 2003;30:1220-30 https://doi.org/10.1007/s00259-003-1212-3
  70. Bohnen NI, Albin RL, Koeppe RA, Wernette KA, Kilbourn MR, Minoshima S, Frey KA. Positron emission tomography of monoaminergic vesicular binding in aging and Parkinson disease. J Cereb Blood Flow Metab 2006;26:1198-212 https://doi.org/10.1038/sj.jcbfm.9600276