Annals of Nuclear Medicine

, Volume 18, Issue 6, pp 453–461 | Cite as

Significance of123I-MIBG scintigraphy as a pathophysiological indicator in the assessment of Parkinson’s disease and related disorders: It can be a specific marker for Lewy body disease

  • Junichi Taki
  • Mitsuhiro Yoshita
  • Masahito Yamada
  • Norihisa Tonami


Recently, reliable and clear evidence for the usefulness of123I-MIBG scintigraphy in the diagnosis of Parkinson’s disease (PD) has been accumulated and it has become increasingly popular as one of the most accurate means of diagnosing the disease. PD, one of the most common neurodegenerative disorders, is characterized by resting tremor, rigidity, bradykinesia or akinesia, and postural instability. The disease is characterized pathologically by distinctive neuronal inclusions called Lewy bodies in many surviving cells of dopaminergic neurons of the substantia nigra pars compacta and other specific brain regions. Furthermore Lewy body type degeneration in the cardiac plexus has been observed in PD. In PD, cardiac MIBG uptake is reduced markedly even in the early disease stages; therefore, MIBG imaging can be used as an indicator of the presence of PD rather than disease severity. Other parkinsonian syndromes such as multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration demonstrate normal cardiac MIBG uptake or only mild reduction of MIBG uptake, indicating that MIBG imaging is a powerful method to differentiate PD from other parkinsonian syndromes. Dementia with Lewy bodies (DLB) also shows severe reduction of MIBG uptake, whereas Alzheimer’s disease (AD) demonstrates normal MIBG uptake, permitting differentiation of DLB from AD using MIBG scintigraphy. In pure autonomic failure, which shares similar pathological findings with PD and is thought to be associated with diffuse loss of sympathetic terminal innervation, cardiac MIBG uptake also decreases markedly. Considering all the data together, marked reduction of cardiac MIBG uptake seems to be a specific marker of Lewy body disease and thus extremely useful in the differentiation from other diseases with similar symptoms without Lewy bodies.

Key words

123I-MIBG Parkinson’s disease Lewy body disease multiple system atrophy dementia with Lewy bodies 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Taki J, Nakajima K, Bunko H, Simizu M, Muramori A, Hisada K. Whole-body distribution of iodine 123 metaiodobenzylguanidine in hypertrophic cardiomyopathy: significance of its washout from the heart.Eur J Nucl Med 1990; 17: 264–268.PubMedCrossRefGoogle Scholar
  2. 2.
    Matsunari I, Bunko H, Taki J, Nakajima K, Muramori A, Kuji I, et al. Regional uptake of iodine-125-metaiodobenzylguanidine in the rat heart.Eur J Nucl Med 1993; 20: 1104–1107.PubMedCrossRefGoogle Scholar
  3. 3.
    Nakajima K, Taki J, Tonami N, Hisada K. Decreased123IMIBG uptake and increased clearance in various cardiac diseases.Nucl Med Commun 1994; 15: 317–323.PubMedCrossRefGoogle Scholar
  4. 4.
    Kreiner G, Wolzt M, Fasching P, Leitha T, Edlmayer A, Korn A, et al. Myocardial m-[123I]iodobenzylguanidine scintigraphy for the assessment of adrenergic cardiac innervation in patients with IDDM. Comparison with cardiovascular reflex tests and relationship to left ventricular function.Diabetes 1995; 44: 543–549.PubMedCrossRefGoogle Scholar
  5. 5.
    Langer A, Freeman MR, Josse RG, Armstrong PW. Metaiodobenzylguanidine imaging in diabetes mellitus: assessment of cardiac sympathetic denervation and its relation to autonomie dysfunction and silent myocardial ischemia.JAm Coll Cardiol 1995; 25: 610–618.CrossRefGoogle Scholar
  6. 6.
    Sakata K, Shirotani M, Yoshida H, Kurata Iodine-123 metaiodobenzylguanidine cardiac imaging to identify and localize vasospastic angina without significant coronary artery narrowing.J Am Coll Cardiol 1997; 30: 370–376.PubMedCrossRefGoogle Scholar
  7. 7.
    Tamaki N, Tadamura E, Kudoh T, Hattori N, Inubushi M, Konishi J. Recent advances in nuclear cardiology in the study of coronary artery disease.Ann Nucl Med 1997; 11: 55–66.PubMedCrossRefGoogle Scholar
  8. 8.
    Matsunari I, Schricke U, Bengel FM, Haase HU, Barthel P, Schmidt G, et al. Extent of cardiac sympathetic neuronal damage is determined by the area of ischemia in patients with acute coronary syndromes.Circulation 2000; 101: 2579–2585.PubMedGoogle Scholar
  9. 9.
    Momose M, Kobayashi H, Ikegami H, Matsuda N, Hachida M, Kasanuki H, et al. Regional cardiac sympathetic reinner-vation in transplanted human hearts detected byI23I-MIBG SPECT imaging.Ann Nucl Med 2000; 14: 333–337.PubMedGoogle Scholar
  10. 10.
    Naruse H, Arii T, Kondo T, Ohnishi M, Sakaki T, Takahashi K, et al. Relation between myocardial response to dobutamine stress and sympathetic nerve activation in patients with idiopathic dilated cardiomyopathy: a comparison of123I- MIBG scintigraphic and echocardiographic data.Ann Nucl Med 2000; 14: 427–432.PubMedGoogle Scholar
  11. 11.
    Sakata Yoshida H, Nawada R, Obayashi K, Tamekiyo H, Mochizuki M. Scintigraphic assessment of regional cardiac sympathetic nervous system in patients with single-vessel coronary artery disease.Ann Nucl Med 2000; 14: 151–158.PubMedGoogle Scholar
  12. 12.
    Koyama K, Inoue T, Hasegawa A, Oriuchi N, Okamoto E, Tomara Y, et al. Alternating myocardial sympathetic neural function of athlete’s heart in professional cycle racers examined with iodine-123-MIBG myocardial scintigraphy.Ann Nucl Med 2001; 15: 307–312.PubMedGoogle Scholar
  13. 13.
    Matsuo S, Nakamura Y, Matsui T, Matsumoto T, Kinoshita M. Detection of denervated but viable myocardium in cardiac sarcoidosis with 1-123 MIBG and Tl-201 SPECT imaging.Ann Nucl Med 2001; 15: 373–375.PubMedGoogle Scholar
  14. 14.
    Nagamachi S, Jinnouchi S, Kurose T, Nishii R, Kawai K, Futami S, et al. Serial change inI23I-MIBG myocardial scintigraphy in non-insulin-dependent diabetes mellitus.Ann Nucl Med 2002; 16: 33–38.PubMedGoogle Scholar
  15. 15.
    Narula J, Zaret BL. Epilogue: development of novel imaging techniques for ultimately superior management of congestive heart failure.J Nucl Cardiol 2002; 9: 81S-86S.PubMedCrossRefGoogle Scholar
  16. 16.
    Shimizu M, Ino H, Yamaguchi M, Terai H, Hayashi Nakajima et al. Heterogeneity of cardiac sympathetic nerve activity and systolic dysfunction in patients with hypertrophic cardiomyopathy.J Nucl Med 2002; 43: 15–20.PubMedGoogle Scholar
  17. 17.
    Hakusui S, Yasuda T, Yanagi T, Tohyama J, Hasegawa Y, Koike Y, et al. A radiological analysis of heart sympathetic functions with meta-[123I]iodobenzylguanidine in neurological patients with autonomic failure.J Auton Nerv Syst 1994; 49: 81–84.PubMedCrossRefGoogle Scholar
  18. 18.
    Ando Y, Obayashi Tanaka Y, Tsuji T, Uchino M, Takahashi M, et al. Radiolabelled metaiodobenzylguanidine in assessment of autonomie dysfunction.Lancet 1994; 343: 984–985.PubMedCrossRefGoogle Scholar
  19. 19.
    Francis GS. Modulation of peripheral sympathetic nerve transmission.J Am Coll Cardiol 1988; 12: 250–254.PubMedCrossRefGoogle Scholar
  20. 20.
    Wieland DM, Brown LE, Rogers WL, Worthington Wu JL, Clinthorne NH, et al. Myocardial imaging with a radioiodinated norepinephrine storage analog.J Nucl Med 1981; 22: 22–31.PubMedGoogle Scholar
  21. 21.
    Nakajo M, Shimabukuro K, Yoshimura H, Yonekura R, Nakabeppu Y, Tanoue P, et al. Iodine-131 metaiodobenzylguanidine intra- and extravesicular accumulation in the rat heart.J Nucl Med 1986; 27: 84–89.PubMedGoogle Scholar
  22. 22.
    Tobes MC, Jaques S Jr, Wieland DM, Sisson JC. Effect of uptake-one inhibitors on the uptake of norepinephrine and metaiodobenzylguanidine.J Nucl Med 1985; 26: 897–907.PubMedGoogle Scholar
  23. 23.
    Dae MW, De Marco T, Botvinick EH, O’Connell JW, Hattner RS, Huberty JP, et al. Scintigraphic assessment of MIBG uptake in globally denervated human and canine hearts—implications for clinical studies.J Nucl Med 1992; 33: 1444–1450.PubMedGoogle Scholar
  24. 24.
    Fagret D, Wolf JE, Vanzetto G, Borrel E. Myocardial uptake of metaiodobenzylguanidine in patients with left ventricular hypertrophy secondary to valvular aortic stenosis.J Nucl Med 1993; 34: 57–60.PubMedGoogle Scholar
  25. 25.
    Sisson JC, Shapiro B, Meyers L, Mallette S, Mangner TJ, Wieland DM, et al. Metaiodobenzylguanidine to map scintigraphically the adrenergic nervous system in man.J Nucl Med 1987; 28: 1625–1636.PubMedGoogle Scholar
  26. 26.
    Manger WM, Hoffman BB. Heart imaging in the diagnosis of pheochromocytoma and assessment of catecholamine uptake.J Nucl Med 1983; 24: 1194–1196.PubMedGoogle Scholar
  27. 27.
    Glowniak JV, Turner FE, Gray LL, Palac RT, Lagunas-Solar MC, Woodward WR. Iodine-123 metaiodobenzylguanidine imaging of the heart in idiopathic congestive cardiomyopathy and cardiac transplants.J Nucl Med 1989; 30: 1182–1191.PubMedGoogle Scholar
  28. 28.
    Sisson JC, Bolgos G, Johnson J. Measuring acute changes in adrenergic nerve activity of the heart in the living animal.Am Heart J 1991; 121: 1119–1123.PubMedCrossRefGoogle Scholar
  29. 29.
    Eisenhofer G, Friberg P, Rundqvist B, Quyyumi AA, Lambert G, Kaye DM, et al. Cardiac sympathetic nerve function in congestive heart failure.Circulation 1996; 93: 1667–1676.PubMedGoogle Scholar
  30. 30.
    Riess O, Kruger R, Schulz JB. Spectram of phenotypes and genotypes in Parkinson’s disease.J Neurol 2002; 249 Suppl 3: III/15–20.Google Scholar
  31. 31.
    Gibb WR, Lees AJ. The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson’s disease.J Neurol Neurosurg Psychiatry 1988; 51: 745–752.PubMedGoogle Scholar
  32. 32.
    Takahashi H, Wakabayashi K. The cellular pathology of Parkinson’s disease.Neuropathology 2001; 21: 315–322.PubMedCrossRefGoogle Scholar
  33. 33.
    Braak H, Del Tredici Bratzke H, Hamm-Clement J, Sandmann-Keil D, Rub U. Staging of the intracerebral inclusion body pathology associated with idiopathic Parkinson’s disease (preclinical and clinical stages).J Neurol 2002; 249 Suppl 3: III/1–5.Google Scholar
  34. 34.
    Braak H, Del Tredici Rub U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson’s disease.Neurobiol Aging 2003; 24: 197–211.PubMedCrossRefGoogle Scholar
  35. 35.
    Braak H, Rub U, Gai WP, Del Tredici Idiopathic Parkinson’s disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen.J Neural Transm 2003; 110: 517–536.PubMedCrossRefGoogle Scholar
  36. 36.
    Wakabayashi K, Takahashi H. Neuropathology of autonomie nervous system in Parkinson’s disease.Eur Neurol 1997; 38 Suppl 2: 2–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Wakabayashi K, Takahashi H, Ohama E, Takeda S, Ikuta F. Lewy bodies in the visceral autonomie nervous system in Parkinson’s disease.Adv Neurol 1993; 60: 609–612.PubMedGoogle Scholar
  38. 38.
    Iwanaga K, Wakabayashi K, Yoshimoto M, Tornita I, Satoh H, Takashima H, et al. Lewy body-type degeneration in cardiac plexus in Parkinson’s and incidental Lewy body diseases.Neurology 1999; 52: 1269–1271.PubMedGoogle Scholar
  39. 39.
    Orimo S, Ozawa E, Oka T, Nakade S, Tsuchiya K, Yoshimoto M, et al. Different histopathology accounting for a decrease in myocardial MIBG uptake in PD and MSA.Neurology 2001; 57: 1140–1141.PubMedGoogle Scholar
  40. 40.
    Orimo S, Oka T, Miura H, Tsuchiya K, Mori F, Wakabayashi K, et al. Sympathetic cardiac denervation in Parkinson’s disease and pure autonomie failure but not in multiple system atrophy.J Neurol Neurosurg Psychiatry 2002; 73: 776–777.PubMedCrossRefGoogle Scholar
  41. 41.
    Yoshita M, Hayashi M, Hirai S. Decreased myocardial accumulation of123I-meta-iodobenzyl guanidine in Parkinson’s disease.Nucl Med Commun 1998; 19: 137–142.PubMedCrossRefGoogle Scholar
  42. 42.
    Taki J, Nakajima K, Hwang EH, Matsunari I, Komai K, Yoshita M, et al. Peripheral sympathetic dysfunction in patients with Parkinson’s disease without autonomie failure is heart selective and disease specific.Eur J Nucl Med 2000; 27: 566–573.PubMedCrossRefGoogle Scholar
  43. 43.
    Takatsu H, Nishida H, Matsuo H, Watanabe S, Nagashima K Wada H, et al. Cardiac sympathetic denervation from the early stage of Parkinson’s disease: clinical and experimental studies with radiolabeled MIBG.J Nucl Med 2000; 41: 71–77.PubMedGoogle Scholar
  44. 44.
    Druschky A, Hilz MJ, Platsch G, Radespiel-Troger M, Druschky K, Kuwert T, et al. Differentiation of Parkinson’s disease and multiple system atrophy in early disease stages by means of I-123-MIBG-SPECT.J Neurol Sci 2000; 175: 3–12.PubMedCrossRefGoogle Scholar
  45. 45.
    Hamada K, Hirayama M, Watanabe H, Kobayashi R, Ito H, leda T, et al. Onset age and severity of motor impairment are associated with reduction of myocardial123I-MIBG uptake in Parkinson’s disease.J Neurol Neurosurg Psychiatry 2003; 74: 423–426.PubMedCrossRefGoogle Scholar
  46. 46.
    Braune S, Reinhardt M, Bathmann J, Krause T, Lehmann M, Lucking CH. Impaired cardiac uptake of meta-[l23I]iodobenzylguanidine in Parkinson’s disease with autonomic failure.Acta Neurol Scand 1998; 97: 307–314.PubMedGoogle Scholar
  47. 47.
    Braune S, Reinhardt M, Schnitzer R, Riedel A, Lucking CH. Cardiac uptake of [123I]MIBG separates Parkinson’s disease from multiple system atrophy.Neurobgy 1999; 53: 1020–1025.Google Scholar
  48. 48.
    Orimo S, Ozawa E, Nakade S, Sugimoto T, Mizusawa H. (123)I-metaiodobenzylguanidine myocardial scintigraphy in Parkinson’s disease.J Neurol Neurosurg Psychiatry 1999; 67: 189–194.PubMedCrossRefGoogle Scholar
  49. 49.
    Courbon F, Brefel-Courbon C, Thalamas C, Alibelli MJ, Berry I, Montastruc JL, et al. Cardiac MIBG scintigraphy is a sensitive tool for detecting cardiac sympathetic denervation in Parkinson’s disease.Mov Disord 2003; 18: 890–897.PubMedCrossRefGoogle Scholar
  50. 50.
    Yoshita M. Differentiation of idiopathic Parkinson’s disease from striatonigral degeneration and progressive supra-nuclear palsy using iodine-123 meta-iodobenzylguanidine myocardial scintigraphy.J Neurol Sci 1998; 155: 60–67.PubMedCrossRefGoogle Scholar
  51. 51.
    Iwasa K, Nakajima K, Yoshikawa H, Tada A, Taki J, Takamori M. Decreased myocardial123I-MIBG uptake in Parkinson’s disease.Acta Neurol Scand 1998; 97: 303–306.PubMedGoogle Scholar
  52. 52.
    Satoh A, Serita T, Seto M, Tornita I, Satoh H, Iwanaga K. et al. Loss ofI23I-MIBG uptake by the heart in Parkinson’s disease: assessment of cardiac sympathetic denervation and diagnostic value.J Nucl Med 1999; 40: 371–375.PubMedGoogle Scholar
  53. 53.
    Goldstein DS, Holmes C, Li ST, Bruce S, Metman LV, Cannon RO, 3rd. Cardiac sympathetic denervation in Parkinson disease.Ann Intern Med 2000; 133: 338–347.PubMedGoogle Scholar
  54. 54.
    Eisenhofer G, Esler MD, Meredith IT, Dart A, Cannon RO 3rd, Quyyumi AA, et al. Sympathetic nervous function in human heart as assessed by cardiac spillovers of dihydroxy-phenylglycol and norepinephrine.Circulation 1992; 85: 1775–1785.PubMedGoogle Scholar
  55. 55.
    Marsden CD. Parkinson’s disease.J Neurol Neurosurg Psychiatry 1994; 57: 672–681.PubMedGoogle Scholar
  56. 56.
    Hughes AJ, Ben-Shlomo Y, Daniel SE, Lees AJ. What features improve the accuracy of clinical diagnosis in Parkinson’s disease: a clinicopathologic study.Neurology 1992; 42: 1142–1146.PubMedGoogle Scholar
  57. 57.
    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: 181–184.PubMedGoogle Scholar
  58. 58.
    Hughes AJ, Daniel SE, Blankson S, Lees AJ. A clinicopathologic study of 100 cases of Parkinson’s disease.Arch Neurol 1993; 50: 140–148.PubMedGoogle Scholar
  59. 59.
    Wenning GK, Litvan I, Jankovic J, Granata R, Mangone CA, McKee A, et al. Natural history and survival of 14 patients with corticobasal degeneration confirmed at postmortem examination.J Neurol Neurosurg Psychiatry 1998; 64: 184–189.PubMedGoogle Scholar
  60. 60.
    Reinhardt MJ, Jungling FD, Krause TM, Braune S. Scinti-graphic differentiation between two forms of primary dys-autonomia early after onset of autonomic dysfunction: value of cardiac and pulmonary iodine-123 MIBG uptake.Eur J Nucl Med 2000; 27: 595–600.PubMedCrossRefGoogle Scholar
  61. 61.
    Takatsu H, Nagashima K, Murase M, Fujiwara H, Nishida H, Matsuo H, et al. Differentiating Parkinson disease from multiple-system atrophy by measuring cardiac iodine-123 metaiodobenzylguanidine accumulation.JAMA 2000; 284: 44–45.PubMedCrossRefGoogle Scholar
  62. 62.
    Jellinger K, Riederer P, Tomonaga M. Progressive supra-nuclear palsy: clinico-pathological and biochemical studies.J Neural Transm Suppl 1980: 111–128.Google Scholar
  63. 63.
    Wenning GK, Ebersbach G, Verny M, Chaudhuri KR, JellingerK McKee A, et al. Progression of falls in postmortem-confirmed parkinsonian disorders.Mov Disord 1999; 14: 947–950.PubMedCrossRefGoogle Scholar
  64. 64.
    Orimo S, Ozawa E, Nakade S, Hattori H, Tsuchiya K, Taki K, et al. [123I] meta-iodobenzylguanidine myocardial scintigraphy differentiates corticobasal degeneration from Parkinson’s disease.Intern Med 2003; 42: 127–128.PubMedCrossRefGoogle Scholar
  65. 65.
    McKeith I, Mintzer J, Aarsland D, Burn D, Chiu H, Cohen-Mansfield J, et al. Dementia with Lewy bodies.Lancet Neurol 2004; 3: 19–28.PubMedCrossRefGoogle Scholar
  66. 66.
    McKeith IG, Perry EK, Perry RH. Report of the second dementia with Lewy body international workshop: diagnosis and treatment. Consortium on Dementia with Lewy Bodies.Neurology 1999; 53: 902–905.PubMedGoogle Scholar
  67. 67.
    Yoshita M, Taki J, Yamada M. A clinical role for [(123)I]MIBG myocardial scintigraphy in the distinction between dementia of the Alzheimer’s-type and dementia with Lewy bodies.J Neurol Neurosurg Psychiatry 2001; 71: 583–588.PubMedCrossRefGoogle Scholar
  68. 68.
    Watanabe H, Ieda T, Katayama T, Takeda A, Aiba I, Doyu M, et al. Cardiac (123)I-meta-iodobenzylguanidine (MIBG) uptake in dementia with Lewy bodies: comparison with Alzheimer’s disease.J Neurol Neurosurg Psychiatry 2001; 70: 781–783.PubMedCrossRefGoogle Scholar
  69. 69.
    Oide T, Tokuda T, Momose M, Oguchi K, Nakamura A, Ohara S, et al. Usefulness of [123I]metaiodobenzylguanidine ([123I]MIBG) myocardial scintigraphy in differentiating between Alzheimer’s disease and dementia with Lewy bodies.Intern Med 2003; 42: 686–690.PubMedCrossRefGoogle Scholar
  70. 70.
    Hishikawa N, Hashizume Y, Yoshida M, Sobue G. Clinical and neuropathological correlates of Lewy body disease.Acta Neuropathol (Beri) 2003; 105: 341–350.Google Scholar
  71. 71.
    Hirayama M, Hakusui S, Koike Y, Ito Kato T, Ikeda M, et al. A scintigraphical qualitative analysis of peripheral vascular sympathetic function with meta-[l23I]iodobenzyl-guanidine in neurological patients with autonomie failure.J Auton Nerv Syst 1995; 53: 230–234.PubMedCrossRefGoogle Scholar
  72. 72.
    Yoshida M, Fukumoto Y, Kuroda Y, Ohkoshi N. Sympathetic denervation of myocardium demonstrated by123I-MIBG scintigraphy in pure progressive autonomie failure.Eur Neurol 1997; 38: 291–296.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2004

Authors and Affiliations

  • Junichi Taki
    • 1
  • Mitsuhiro Yoshita
    • 2
  • Masahito Yamada
    • 2
  • Norihisa Tonami
    • 1
  1. 1.Departments of Biotracer MedicineKanazawa University Graduate School of Medical SciencesKanazawaJapan
  2. 2.Departments of Neurology and Neurobiology of AgingKanazawa University Graduate School of Medical SciencesJapan

Personalised recommendations