Assessment of anthracycline-related myocardial adrenergic derangement by [123i]metaiodobenzylguanidine scintigraphy

Abstract

Myocardial adrenergic neuron integrity and function were evaluated in 21 patients who had received doxorubicin or epirubicin for various malignancies. Myocardial uptake of iodine-123 metaiodobenzylguanidine ([123I]MIBG), a marker suitable for the study of myocardial neuron injury, was calculated from planar scintigraphic images after 4 h and the washout between 15 min and 4 h. In 13 patients with normal left ventricle ejection fraction (LVEF) analysed at three cumulative dose levels (no, low and middle dose), [123I]MIBG uptake tended to be significantly impaired (z = -2.772, P = 0.0056), at higher cumulative dose levels, before significant LVEF changes were observed. [123I]MIBG values were considerably decreased in 2/7 patients investigated at low cumulative dose and in 3/8 cases at the middle dose level. On follow-up, 1 of these patients, who had normal LVEF after completion of chemotherapy but whose [123I]MIBG values had progressively deteriorated during anthracycline therapy, subsequently developed congestive heart failure; another patient, whose [123I]MIBG values were impaired at the middle dose level, developed persistent reduced LVEF 5 months after completing therapy. In 8 patients, who had developed persistently, reduced LVEF at high doxorubicin cumulative dose levels, [123I]MIBG, performed in the period after chemotherapy discontinuation, was invariably abnormal. These data suggest that myocardial adrenergic derangement plays a role in anthracycline-associated cardiotoxicity: its appearance, even at low cumulative anthracycline dose levels, may reflect impairment of the intravesicular norepinephrine storage by incipient anthracycline-associated cardiac neuron injury. [123I]MIBG scintigraphy may be useful to assess myocardial adrenergic derangement during and in the follow-up of anthracycline therapy and potentially detect patients who are at risk.