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

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/M_early and H/M_late) 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/M_early. 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; cardiotoxicity; doxorubicin; lymphoma; sympathetic nervous system.