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123I-MIBG for detection of subacute doxorubicin-induced cardiotoxicity in patients with malignant lymphoma

  • Adam Høgsbro LaursenEmail author
  • Rasmus Sejersten Ripa
  • Philip Hasbak
  • Andreas Kjær
  • Marie Bayer Elming
  • Lars Køber
  • Martin Hutchings
  • Jens Jakob Thune
Original Article

Abstract

Background

Doxorubicin is the mainstay of curative lymphoma treatment but is associated with a dose-dependent cardiotoxicity that is often recognized too late to avoid substantial irreversible cardiac injury. Iodine-123 metaiodobenzylguanidine (123I-MIBG) is a gamma-emitting tracer that mimics noradrenaline uptake, storage, and release mechanisms in adrenergic presynaptic neurons. 123I-MIBG scintigraphy can be used for assessment of doxorubicin-induced injury to myocardial adrenergic neurons during treatment and could be the tool for early detection of doxorubicin cardiotoxicity, which is currently lacking.

Methods and Results

A total of 37 lymphoma patients scheduled for doxorubicin treatment were included in our study. 123I-MIBG imaging was performed prior to chemotherapy and after a median of 4 cycles of doxorubicin. Early and late heart-to-mediastinum ratios (H/Mearly and H/Mlate) and washout rate (WOR) were used for evaluation of cardiotoxicity. The prognostic value of 123I-MIBG results was assessed using left ventricular ejection fraction (LVEF) as measured by cardiac magnetic resonance at 1-year follow-up. We found a post-therapy increase in WOR (including nine patients with > 10% increase), which was not statistically significant (18.6 vs 23.4%, P = 0.09). The difference appeared to be driven by an increase in H/Mearly. LVEF decreased from baseline to 1-year follow-up (64 vs 58%, P = 0.03). LVEF change was not associated with changes in WOR (P = 0.5).

Conclusion

The present study does not provide evidence for 123I-MIBG imaging as a clinically applicable tool for early detection of doxorubicin-induced cardiotoxicity.

Keywords

123I-MIBG sympathetic nervous system cardiotoxicity doxorubicin lymphoma 

Abbreviations

123I-MIBG

Iodine-123 metaiodobenzylguanidine

CMR

Cardiac magnetic resonance

H/Mearly

Early heart-to-mediastinum ratio

H/Mlate

Late heart-to-mediastinum ratio

LVEF

Left ventricular ejection fraction

WOR

Washout rate

Notes

Disclosure

The authors have no conflicts of interest to declare

Supplementary material

12350_2018_1566_MOESM1_ESM.docx (20 kb)
Supplementary material 1 (DOCX 19 kb)
12350_2018_1566_MOESM2_ESM.pptx (228 kb)
Supplementary material 2 (PPTX 227 kb)

References

  1. 1.
    Chatterjee K, Zhang J, Honbo N, Karliner JS. Doxorubicin cardiomyopathy. Cardiology. 2010;115:155-62.CrossRefGoogle Scholar
  2. 2.
    de Geus-Oei L-F, Mavinkurve-Groothuis AMC, Bellersen L, Gotthardt M, Oyen WJG, Kapusta L, et al. Scintigraphic techniques for early detection of cancer treatment-induced cardiotoxicity. J Nucl Med. 2011;52:560-71.Google Scholar
  3. 3.
    Lekakis J, Prassopoulos V, Athanassiadis P, Kostamis P, Moulopoulos S. Doxorubicin-induced cardiac neurotoxicity: Study with iodine 123-labeled metaiodobenzyiguanidine scintigraphy. J Nucl Cardiol. 1996;3:37-41.CrossRefGoogle Scholar
  4. 4.
    Flotats A, Carrió I. Cardiac neurotransmission SPECT imaging. J Nucl Cardiol. 2004;11:587-602.CrossRefGoogle Scholar
  5. 5.
    D’Amore C, Gargiulo P, Paolillo S, Pellegrino AM, Formisano T, Mariniello A, et al. Nuclear imaging in detection and monitoring of cardiotoxicity. World J Radiol. 2014;6:486-92.CrossRefGoogle Scholar
  6. 6.
    Gupta S, Amanullah A. Radionuclide imaging of cardiac sympathetic innervation in heart failure : unlocking untapped potential. Hear Fail Rev. 2015;20:215-26.CrossRefGoogle Scholar
  7. 7.
    Higuchi T, Schwaiger M. Imaging cardiac neuronal function and dysfunction. Curr Cardiol Rep. 2006;8:131-8.CrossRefGoogle Scholar
  8. 8.
    Christensen TE, Kjaer A, Hasbak P. The clinical value of cardiac sympathetic imaging in heart failure. Clin Physiol Funct Imaging. 2014;34:178-82.CrossRefGoogle Scholar
  9. 9.
    Wakabayashi T, Nakata T, Hashimoto A, Yuda S, Tsuchihashi K, Travin MI, et al. Assessment of underlying etiology and cardiac sympathetic innervation to identify patients at high risk of cardiac death. J Nucl Med. 2001;42:1757-67.Google Scholar
  10. 10.
    Agostini D, Verberne HJ, Burchert W, Knuuti J, Povinec P, Sambuceti G, et al. I-123- mIBG myocardial imaging for assessment of risk for a major cardiac event in heart failure patients : insights from a retrospective European multicenter study. Eur J Nucl Med Mol Imaging. 2008;35:535-46.CrossRefGoogle Scholar
  11. 11.
    Nakata T, Nakajima K, Yamashina S, Yamada T, Momose M, Kasama S, et al. A pooled analysis of multicenter cohort studies of 123I-mIBG imaging of sympathetic innervation for assessment of long-term prognosis in heart failure. JACC Cardiovasc Imaging. 2013;6:772-84.CrossRefGoogle Scholar
  12. 12.
    Ogita H, Shimonagata T, Fukunami M, Kumagai K, Yamada T, Asano Y, et al. Prognostic significance of cardiac 123-I metaiodobenzylguanidine imaging for mortality and morbidity in patients with chronic heart failure : A prospective study. Heart. 2001;86:656-60.CrossRefGoogle Scholar
  13. 13.
    Carrio I, Estorch M, Bernã L, López-Pousa J, Tabernero J, Torres G. Indium-111-antimyosin and iodine-123-MIBG studies in early assessment of doxorubicin cardiotoxicity. J Nucl Med. 1995;36:2044-9.Google Scholar
  14. 14.
    Valdés Olmos RA, Bokkel Huinink WW, Hoeve RFA, van Tinteren H, Bruning PF, et al. Assessment of anthracycline-related myocardial adrenergic derangement by [1231] metaiodobenzylguanidine scintigraphy. Eur J Cancer. 1995;31:26-31.CrossRefGoogle Scholar
  15. 15.
    Flotats A, Carrió I, Agostini D, Le Guludec D, Marcassa C, Schaffers M, et al. Proposal for standardization of 123 I-metaiodobenzylguanidine (MIBG) cardiac sympathetic imaging by the EANM Cardiovascular Committee and the European Council of Nuclear Cardiology. Eur J Nucl Med Mol Imaging. 2010;37:1802-12.CrossRefGoogle Scholar
  16. 16.
    Laursen AH, Thune JJ, Hutchings M, Hasbak P, Kjær A, Elming MB, et al. I-MIBG imaging for detection of anthracycline-induced cardiomyopathy. Clin Physiol Funct Imaging. 2018;38:176-85.CrossRefGoogle Scholar
  17. 17.
    Cardinale D, Colombo A, Bacchiani G, Tedeschi I, Meroni CA, Veglia F, et al. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation. 2015;131:1981-8.CrossRefGoogle Scholar
  18. 18.
    Dansk Cardiologisk Selskab. Kardiologisk håndtering af cancerpatienter før, under og efter behandling med kardiotoksiske antineoplastika og stråleterapi. 2016;1-9.Google Scholar
  19. 19.
    Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 2014;117:501-32.CrossRefGoogle Scholar
  20. 20.
    Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127:2375-90.CrossRefGoogle Scholar
  21. 21.
    Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, et al. Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification. J Clin Oncol. 2018;32:3059-68.CrossRefGoogle Scholar
  22. 22.
    Volkova M, Russell R. Anthracycline cardiotoxicity : prevalence, pathogenesis and treatment. Curr Cardiol Rev. 2011;7:214-20.CrossRefGoogle Scholar
  23. 23.
    Glass CK, Mitchell RN. Winning the battle, but losing the war: Mechanisms and morphology of cancer-therapy-associated cardiovascular toxicity. Cardiovasc Pathol. 2017;30:55-63.CrossRefGoogle Scholar
  24. 24.
    Estorch M, Carrió I, Berná L, López-Pousa J, Torres G. Myocardial iodine-labeled metaiodobenzylguanidine 123 uptake relates to age. J Nucl Cardiol. 1995;2:126-32.Google Scholar
  25. 25.
    R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org/. 2015.
  26. 26.
    Somsen GA, Verberne HJ, Fleury E, Righetti A. Normal values and within-subject variability of cardiac I-123 MIBG scintigraphy in healthy individuals : implications for clinical studies. J Nucl Cardiol. 2004;11:126-33.CrossRefGoogle Scholar
  27. 27.
    Oliveira GH, Al-Kindi SG, Caimi PF, Lazarus HM. Maximizing anthracycline tolerability in hematologic malignancies: Treat to each heart’s content. Blood Rev. 2016;30:169-78.CrossRefGoogle Scholar
  28. 28.
    Wakasugi S, Fischman AJ, Babich JW, Aretz HT, Callahan RJ, Nakaki M, et al. Metaiodobenzylguanidine : Evaluation of its potential as a tracer for monitoring doxorubicin cardiomyopathy. J Nucl Med. 1993;34:1282-6.Google Scholar
  29. 29.
    Jeon TJ, Lee JD, Ha J, Yang WI, Cho SH. Evaluation of cardiac adrenergic neuronal damage in rats with doxorubicin-induced cardiomyopathy using iodine-131 MIBG autoradiography and PGP 95 immunohistochemistry. Eur J Nucl Med. 2000;27:686-93.CrossRefGoogle Scholar
  30. 30.
    Takano H, Ozawa H, Kobayashi I, Hamaoka S, Nakajima A, Nakamura T, et al. Atrophic nerve fibers in regions of reduced MIBG uptake in doxorubicin cardiomyopathy. J Nucl Med. 1995;36:2060-1.Google Scholar
  31. 31.
    Verberne HJ, Brewster LM, Somsen GA, van Eck-Smit BLF. Prognostic value of myocardial 123 I-metaiodobenzylguanidine (MIBG) parameters in patients with heart failure: A systematic review. Eur Heart J. 2008;29:1147-59.CrossRefGoogle Scholar
  32. 32.
    Nakata T, Miyamoto K, Doi A, Sasao H, Wakabayashi T, Kobayashi H, et al. Cardiac death prediction and impaired cardiac sympathetic innervation assessed by MIBG in patients with failing and nonfailing hearts. J Nucl Cardiol. 1998;5:579-90.CrossRefGoogle Scholar
  33. 33.
    Wakasugi S, Wada A, Hasegawa Y, Nakano S, Shibata N. Detection of abnormal cardiac adrenergic neuron activity in adriamycin-induced cardiomyopathy with Iodine-125-metaiodobenzylguanidine. J Nucl Med. 1992;33:208-14.Google Scholar
  34. 34.
    Sakata K, Shirotani M, Yoshida H, Kurata C. Physiological fluctuation of the human left ventricle sympathetic nervous system assessed by iodine-123-MIBG nervous system pathophysiology has pro. J Nucl Med. 1998;39:1667-71.Google Scholar
  35. 35.
    Sakata K, Iida K, Mochizuki N, Ito M, Nakaya Y. Physiological changes in human cardiac sympathetic innervation and activity assessed by 123 I-metaiodobenzylguanidine (MIBG) imaging. Circ J. 2009;73:310-5.CrossRefGoogle Scholar
  36. 36.
    dos Santos MJ, da Rocha ET, Verberne HJ, da Silva ET, Aragon DC, Junior JS. Assessment of late anthracycline-induced cardiotoxicity by 123I-mIBG cardiac scintigraphy in patients treated during childhood and adolescence. J Nucl Cardiol. 2015;24:1-9.Google Scholar
  37. 37.
    Paolillo S, Rengo G, Pagano G, Pellegrino T, Savarese G, Femminella GD, et al. Impact of diabetes on cardiac sympathetic innervation in patients with heart failure. Diabetes Care. 2013;36:2395-401.CrossRefGoogle Scholar
  38. 38.
    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. Park Relat Disord. 2012;18:494-500.CrossRefGoogle Scholar
  39. 39.
    Carrio I, Cowie MR, Yamazaki J, Udelson J, Camici PG. Cardiac sympathetic imaging with mIBG in heart failure. JACC Cardiovasc Imaging. 2010;3:92-100.CrossRefGoogle Scholar
  40. 40.
    Valdes Olmos RA, Huinink WW, Dewit LGH, Hoefnagel CA, Liem IH, van Tinteren H. Iodine-123 metaiodobenzylguanidine in the assessment of late cardiac effects from cancer therapy. Eur J Nucl Med. 1996;23:453-8.CrossRefGoogle Scholar

Copyright information

© American Society of Nuclear Cardiology 2018

Authors and Affiliations

  • Adam Høgsbro Laursen
    • 1
    Email author
  • Rasmus Sejersten Ripa
    • 2
  • Philip Hasbak
    • 2
  • Andreas Kjær
    • 2
  • Marie Bayer Elming
    • 3
  • Lars Køber
    • 3
  • Martin Hutchings
    • 1
  • Jens Jakob Thune
    • 3
    • 4
  1. 1.Department of Hematology, RigshospitaletUniversity of CopenhagenCopenhagenDenmark
  2. 2.Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, RigshospitaletUniversity of CopenhagenCopenhagenDenmark
  3. 3.Department of Cardiology, RigshospitaletUniversity of CopenhagenCopenhagenDenmark
  4. 4.Department of Cardiology, Bispebjerg and Frederiksberg HospitalUniversity of CopenhagenCopenhagenDenmark

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