123I-MIBG for detection of subacute doxorubicin-induced cardiotoxicity in patients with malignant lymphoma
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).
The present study does not provide evidence for 123I-MIBG imaging as a clinically applicable tool for early detection of doxorubicin-induced cardiotoxicity.
Keywords123I-MIBG sympathetic nervous system cardiotoxicity doxorubicin lymphoma
Cardiac magnetic resonance
Early heart-to-mediastinum ratio
Late heart-to-mediastinum ratio
Left ventricular ejection fraction
The authors have no conflicts of interest to declare
- 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
- 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.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
- 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
- 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
- 18.Dansk Cardiologisk Selskab. Kardiologisk håndtering af cancerpatienter før, under og efter behandling med kardiotoksiske antineoplastika og stråleterapi. 2016;1-9.Google Scholar
- 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.R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org/. 2015.
- 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
- 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
- 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.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
- 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