Top

Published in:

01-12-2021 | Parkinson's Disease | Original research

Dynamic planar scintigraphy for the rapid kinetic measurement of myocardial ¹²³I-MIBG turnover can identify Lewy body disease

Authors: Yoshitaka Kumakura, Yuji Shimizu, Masatsugu Hariu, Ken-ichi Ichikawa, Norihito Yoshida, Masato Suzuki, Satoru Oji, Shinya Narukawa, Haruo Yoshimasu, Kyoichi Nomura

Published in: EJNMMI Research | Issue 1/2021

Abstract

Background

Using two static scans for ¹²³I-meta-iodobenzyl-guanidine (¹²³I-MIBG) myocardial scintigraphy ignores the dynamic response from vesicular trapping in nerve terminals. Moreover, the long pause between scans is impractical for patients with Lewy body diseases (LBDs). Here, we optimized indices that capture norepinephrine kinetics, tested their diagnostic performance, and determined the differences in ¹²³I-MIBG performance among disease groups.

Methods

We developed a new 30-min protocol for ¹²³I-MIBG dynamic planar imaging for suspected LBD patients. Pharmacokinetic modelling of time-activity curves (TACs) was used to calculate three new indices: unidirectional uptake of ¹²³I-MIBG to vesicular trapping (iUp), rate of myocardial ¹²³I-MIBG loss (iLoss), and non-specific fractional distribution of ¹²³I-MIBG in the interstitial space. We compared the performance of the new and existing indices with regard to discrimination of patients with or without LBDs. Subgroup analysis was performed to examine differences in ¹²³I-MIBG turnover between patients in a dementia with Lewy bodies (DLB) group and two Parkinson’s disease (PD) groups, one with and the other without REM sleep behaviour disorder (RBD).

Results

iLoss was highly discriminative, particularly for patients with low myocardial ¹²³I-MIBG trapping, and the new indices outperformed existing ones. ROC analysis revealed that the AUC of iLoss (0.903) was significantly higher than that of early HMR (0.863), while comparable to that of delayed HMR (0.892). The RBD-positive PD group and the DLB group had higher turnover rates than the RBD-negative PD group, indicating a potential association between prognosis and iLoss.

Conclusion

¹²³I-MIBG turnover can be quantified in 30 min using a three-parameter model based on ¹²³I-MIBG TACs. The discriminatory performance of the new model-based indices might help explain the neurotoxicity or neurodegeneration that occurs in LBD patients.

Available only for authorised users

Orimo S, Amino T, Itoh Y, et al. Cardiac sympathetic denervation precedes neuronal loss in the sympathetic ganglia in Lewy body disease. Acta Neuropathol. 2005;109:583–8. https://doi.org/10.1007/s00401-005-0995-7.CrossRefPubMed

McKeith IG, Boeve BF, Dickson DW, et al. Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB Consortium. Neurology. 2017;89:88–100. https://doi.org/10.1212/WNL.0000000000004058.CrossRefPubMedPubMedCentral

Orimo S, Yogo M, Nakamura T, Suzuki M, Watanabe H. (123)I-meta-iodobenzylguanidine (MIBG) cardiac scintigraphy in alpha-synucleinopathies. Ageing Res Rev. 2016;30:122–33. https://doi.org/10.1016/j.arr.2016.01.001.CrossRefPubMed

Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord. 2015;30:1591–601. https://doi.org/10.1002/mds.26424.CrossRefPubMed

Takahashi M, Ikemura M, Oka T, et al. Quantitative correlation between cardiac MIBG uptake and remaining axons in the cardiac sympathetic nerve in Lewy body disease. J Neurol Neurosurg Psychiatry. 2015;86:939–44. https://doi.org/10.1136/jnnp-2015-310686.CrossRefPubMed

King AE, Mintz J, Royall DR. Meta-analysis of 123I-MIBG cardiac scintigraphy for the diagnosis of Lewy body-related disorders. Mov Disord. 2011;26:1218–24. https://doi.org/10.1002/mds.23659.CrossRefPubMed

Orimo S, Suzuki M, Inaba A, Mizusawa H. 123I-MIBG myocardial scintigraphy for differentiating Parkinson’s disease from other neurodegenerative parkinsonism: a systematic review and meta-analysis. Parkinsonism Relat Disord. 2012;18:494–500. https://doi.org/10.1016/j.parkreldis.2012.01.009.CrossRefPubMed

Treglia G, Cason E. Diagnostic performance of myocardial innervation imaging using MIBG scintigraphy in differential diagnosis between dementia with lewy bodies and other dementias: a systematic review and a meta-analysis. J Neuroimaging. 2012;22:111–7. https://doi.org/10.1111/j.1552-6569.2010.00532.x.CrossRefPubMed

Treglia G, Cason E, Stefanelli A, et al. MIBG scintigraphy in differential diagnosis of Parkinsonism: a meta-analysis. Clin Auton Res. 2012;22:43–55. https://doi.org/10.1007/s10286-011-0135-5.CrossRefPubMed

10.

Yoshita M, Arai H, Arai H, et al. Diagnostic accuracy of 123I-meta-iodobenzylguanidine myocardial scintigraphy in dementia with Lewy bodies: a multicenter study. PLoS ONE. 2015;10:e0120540. https://doi.org/10.1371/journal.pone.0120540.CrossRefPubMedPubMedCentral

11.

Komatsu J, Samuraki M, Nakajima K, et al. (123)I-MIBG myocardial scintigraphy for the diagnosis of DLB: a multicentre 3-year follow-up study. J Neurol Neurosurg Psychiatry. 2018;89:1167–73. https://doi.org/10.1136/jnnp-2017-317398.CrossRefPubMed

12.

Manabe Y, Inui Y, Toyama H, Kosaka K. 123I-metaiodobenzylguanidine myocardial scintigraphy with early images alone is useful for the differential diagnosis of dementia with Lewy bodies. Psychiatry Res Neuroimaging. 2017;261:75–9. https://doi.org/10.1016/j.pscychresns.2016.12.011.CrossRefPubMed

13.

Raffel DM, Corbett JR, del Rosario RB, et al. Clinical evaluation of carbon-11-phenylephrine: MAO-sensitive marker of cardiac sympathetic neurons. J Nucl Med. 1996;37:1923–31.PubMed

14.

Harms HJ, de Haan S, Knaapen P, et al. Quantification of [(11)C]-meta-hydroxyephedrine uptake in human myocardium. EJNMMI Res. 2014;4:52. https://doi.org/10.1186/s13550-014-0052-4.CrossRefPubMedPubMedCentral

15.

Schwaiger M, Kalff V, Rosenspire K, et al. Noninvasive evaluation of sympathetic nervous system in human heart by positron emission tomography. Circulation. 1990;82:457–64. https://doi.org/10.1161/01.cir.82.2.457.CrossRefPubMed

16.

Sinusas AJ, Lazewatsky J, Brunetti J, et al. Biodistribution and radiation dosimetry of LMI1195: first-in-human study of a novel 18F-labeled tracer for imaging myocardial innervation. J Nucl Med. 2014;55:1445–51. https://doi.org/10.2967/jnumed.114.140137.CrossRefPubMed

17.

Jang KS, Jung YW, Gu G, et al. 4-[18F]Fluoro-m-hydroxyphenethylguanidine: a radiopharmaceutical for quantifying regional cardiac sympathetic nerve density with positron emission tomography. J Med Chem. 2013;56:7312–23. https://doi.org/10.1021/jm400770g.CrossRefPubMedPubMedCentral

18.

Raffel DM, Jung YW, Koeppe RA, et al. First-in-human studies of [(18)F] fluorohydroxyphenethylguanidines. Circ Cardiovasc Imaging. 2018;11: e007965. https://doi.org/10.1161/CIRCIMAGING.118.007965.CrossRefPubMedPubMedCentral

19.

Ding YS, Fowler JS, Dewey SL, et al. Comparison of high specific activity (-) and (+)-6-[18F]fluoronorepinephrine and 6-[18F]fluorodopamine in baboons: heart uptake, metabolism and the effect of desipramine. J Nucl Med. 1993;34:619–29.PubMed

20.

Goldstein DS, Coronado L, Kopin IJ. 6-[Fluorine-18]fluorodopamine pharmacokinetics and dosimetry in humans. J Nucl Med. 1994;35:964–73.PubMed

21.

Li ST, Holmes C, Kopin IJ, Goldstein DS. Aging-related changes in cardiac sympathetic function in humans, assessed by 6–18F-fluorodopamine PET scanning. J Nucl Med. 2003;44:1599–603.PubMed

22.

Goldstein DS, Holmes C, Sullivan P, et al. Deficient vesicular storage: a common theme in catecholaminergic neurodegeneration. Parkinsonism Relat Disord. 2015;21:1013–22. https://doi.org/10.1016/j.parkreldis.2015.07.009.CrossRefPubMedPubMedCentral

23.

Anang JB, Gagnon JF, Bertrand JA, et al. Predictors of dementia in Parkinson disease: a prospective cohort study. Neurology. 2014;83:1253–60. https://doi.org/10.1212/WNL.0000000000000842.CrossRefPubMedPubMedCentral

24.

Postuma RB, Bertrand JA, Montplaisir J, et al. Rapid eye movement sleep behavior disorder and risk of dementia in Parkinson’s disease: a prospective study. Mov Disord. 2012;27:720–6. https://doi.org/10.1002/mds.24939.CrossRefPubMed

25.

Stiasny-Kolster K, Mayer G, Schäfer S, Möller JC, Heinzel-Gutenbrunner M, Oertel WH. The REM sleep behavior disorder screening questionnaire—a new diagnostic instrument. Mov Disord. 2007;22:2386–93. https://doi.org/10.1002/mds.21740.CrossRefPubMed

26.

Postuma RB, Arnulf I, Hogl B, et al. A single-question screen for rapid eye movement sleep behavior disorder: a multicenter validation study. Mov Disord. 2012;27:913–6. https://doi.org/10.1002/mds.25037.CrossRefPubMedPubMedCentral

27.

Okuda K, Nakajima K, Hosoya T, et al. Semi-automated algorithm for calculating heart-to-mediastinum ratio in cardiac Iodine-123 MIBG imaging. J Nucl Cardiol. 2011;18:82–9. https://doi.org/10.1007/s12350-010-9313-4.CrossRefPubMed

28.

Wu J, Lin SF, Gallezot JD, et al. Quantitative analysis of dynamic 123I-mIBG SPECT imaging data in healthy humans with a population-based metabolite correction method. J Nucl Med. 2016;57:1226–32. https://doi.org/10.2967/jnumed.115.171710.CrossRefPubMed

29.

Akaike H. A new look at the statistical model identification. IEEE Trans Autom Control. 1974;19:716–23. https://doi.org/10.1109/TAC.1974.1100705.CrossRef

30.

Schwarz G. Estimating the dimension of a model. Ann Stat. 1978;6:461–4.CrossRef

31.

Cortes C, Vapnik V. Support-vector networks. Mach Learn. 1995;20:273–97. https://doi.org/10.1007/BF00994018.CrossRef

32.

Chawla NV, Bowyer KW, Hall LO, Kegelmeyer WP. SMOTE: synthetic minority over-sampling technique. J Artif Intell Res. 2002;16:321–57. https://doi.org/10.1613/jair.953.CrossRef

33.

Kumakura Y, Cumming P, Vernaleken I, et al. Elevated [18F]fluorodopamine turnover in brain of patients with schizophrenia: an [18F]fluorodopa/positron emission tomography study. J Neurosci. 2007;27:8080–7. https://doi.org/10.1523/JNEUROSCI.0805-07.2007.CrossRefPubMedPubMedCentral

34.

Kumakura Y, Vernaleken I, Grunder G, Bartenstein P, Gjedde A, Cumming P. PET studies of net blood-brain clearance of FDOPA to human brain: age-dependent decline of [18F]fluorodopamine storage capacity. J Cereb Blood Flow Metab. 2005;25:807–19. https://doi.org/10.1038/sj.jcbfm.9600079.CrossRefPubMed

35.

Pereira RS, Wisenberg G, Prato FS, Yvorchuk K. Clinical assessment of myocardial viability using MRI during a constant infusion of Gd-DTPA. MAGMA. 2000;11:104–13. https://doi.org/10.1007/bf02678473.CrossRefPubMed

36.

Goldstein DS, Holmes C, Kopin IJ, Sharabi Y. Intra-neuronal vesicular uptake of catecholamines is decreased in patients with Lewy body diseases. J Clin Invest. 2011;121:3320–30. https://doi.org/10.1172/JCI45803.CrossRefPubMedPubMedCentral

37.

Goldstein DS, Pekker MJ, Eisenhofer G, Sharabi Y. Computational modeling reveals multiple abnormalities of myocardial noradrenergic function in Lewy body diseases. JCI Insight. 2019. https://doi.org/10.1172/jci.insight.130441.CrossRefPubMedPubMedCentral

38.

Ingelsson M. Alpha-synuclein oligomers-neurotoxic molecules in Parkinson’s disease and other Lewy body disorders. Front Neurosci. 2016;10:408. https://doi.org/10.3389/fnins.2016.00408.CrossRefPubMedPubMedCentral

39.

Bridi JC, Hirth F. Mechanisms of alpha-synuclein induced synaptopathy in Parkinson’s disease. Front Neurosci. 2018;12:80. https://doi.org/10.3389/fnins.2018.00080.CrossRefPubMedPubMedCentral

40.

Ghiglieri V, Calabrese V, Calabresi P. Alpha-synuclein: from early synaptic dysfunction to neurodegeneration. Front Neurol. 2018;9:295. https://doi.org/10.3389/fneur.2018.00295.CrossRefPubMedPubMedCentral

41.

Masato A, Plotegher N, Boassa D, Bubacco L. Impaired dopamine metabolism in Parkinson’s disease pathogenesis. Mol Neurodegener. 2019;14:35. https://doi.org/10.1186/s13024-019-0332-6.CrossRefPubMedPubMedCentral

42.

Eisenhofer G, Kopin IJ, Goldstein DS. Catecholamine metabolism: a contemporary view with implications for physiology and medicine. Pharmacol Rev. 2004;56:331–49. https://doi.org/10.1124/pr.56.3.1.CrossRefPubMed

43.

Goldstein DS. The catecholaldehyde hypothesis: where MAO fits in. J Neural Transm (Vienna). 2020;127:169–77. https://doi.org/10.1007/s00702-019-02106-9.CrossRef

44.

Kim JS, Park HE, Oh YS, et al. Orthostatic hypotension and cardiac sympathetic denervation in Parkinson disease patients with REM sleep behavioral disorder. J Neurol Sci. 2016;362:59–63. https://doi.org/10.1016/j.jns.2016.01.020.CrossRefPubMed

45.

Miyamoto T, Miyamoto M, Iwanami M, Hirata K. Cardiac 123I-MIBG accumulation in Parkinson’s disease differs in association with REM sleep behavior disorder. Parkinsonism Relat Disord. 2011;17:219–20. https://doi.org/10.1016/j.parkreldis.2010.11.020.CrossRefPubMed

46.

Gabilondo I, Llorens V, Rodriguez T, et al. Myocardial MIBG scintigraphy in genetic Parkinson’s disease as a model for Lewy body disorders. Eur J Nucl Med Mol Imaging. 2019;46:376–84. https://doi.org/10.1007/s00259-018-4183-0.CrossRefPubMed

47.

Fujishiro H, Okuda M, Iwamoto K, et al. Early diagnosis of Lewy body disease in patients with late-onset psychiatric disorders using clinical history of rapid eye movement sleep behavior disorder and [(123) I]-metaiodobenzylguanidine cardiac scintigraphy. Psychiatry Clin Neurosci. 2018;72:423–34. https://doi.org/10.1111/pcn.12651.CrossRefPubMed

48.

Savica R, Grossardt BR, Bower JH, et al. Survival and causes of death among people with clinically diagnosed synucleinopathies with parkinsonism: a population-based study. JAMA Neurol. 2017;74:839–46. https://doi.org/10.1001/jamaneurol.2017.0603.CrossRefPubMedPubMedCentral

49.

Stubendorff K, Aarsland D, Minthon L, Londos E. The impact of autonomic dysfunction on survival in patients with dementia with Lewy bodies and Parkinson’s disease with dementia. PLoS ONE. 2012;7:e45451. https://doi.org/10.1371/journal.pone.0045451.CrossRefPubMedPubMedCentral

50.

Pagano G, De Micco R, Yousaf T, Wilson H, Chandra A, Politis M. REM behavior disorder predicts motor progression and cognitive decline in Parkinson disease. Neurology. 2018;91:e894–905. https://doi.org/10.1212/WNL.0000000000006134.CrossRefPubMed

Title: Dynamic planar scintigraphy for the rapid kinetic measurement of myocardial 123I-MIBG turnover can identify Lewy body disease
Authors: Yoshitaka Kumakura
Yuji Shimizu
Masatsugu Hariu
Ken-ichi Ichikawa
Norihito Yoshida
Masato Suzuki
Satoru Oji
Shinya Narukawa
Haruo Yoshimasu
Kyoichi Nomura
Publication date: 01-12-2021
Publisher: Springer Berlin Heidelberg
Keywords: Parkinson's Disease
Scintigraphy
Published in: EJNMMI Research / Issue 1/2021
Electronic ISSN: 2191-219X
DOI: https://doi.org/10.1186/s13550-021-00864-w

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Dynamic planar scintigraphy for the rapid kinetic measurement of myocardial ¹²³I-MIBG turnover can identify Lewy body disease

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2021

Muscarinic inhibition of salivary glands with glycopyrronium bromide does not reduce the uptake of PSMA-ligands or radioiodine

Retraction Note to: Inter- and intraobserver agreement of the quantitative assessment of [99mTc]-labelled anti-programmed death-ligand 1 (PD-L1) SPECT/CT in non-small cell lung cancer

Predicting the nature of pleural effusion in patients with lung adenocarcinoma based on 18F-FDG PET/CT

Rationale for MYC imaging and targeting in pancreatic cancer

CERMEP-IDB-MRXFDG: a database of 37 normal adult human brain [18F]FDG PET, T1 and FLAIR MRI, and CT images available for research

[18F]FDG PET/MRI enables early chemotherapy response prediction in pancreatic ductal adenocarcinoma