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

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 (I-123-MIBG) is a gamma-emitting tracer that mimics noradrenaline uptake, storage, and release mechanisms in adrenergic presynaptic neurons.I-123-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.I-123-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)andH/M-late) and washout rate (WOR) were used for evaluation of cardiotoxicity. The prognostic value of(123)I-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 inH/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(123)I-MIBG imaging as a clinically applicable tool for early detection of doxorubicin-induced cardiotoxicity.